Demystifying Medicine 2013 – Turner’s Syndrome: The X Chromosome Air date: Tuesday, April 02, 2013, 4:00:00 PM The Demystifying Medicine Series, which is …
>> WE'LL GET STARTED.
IT WILL BE INTERESTING TO KNOW,
ONE OF OUR SPEAKERS FOR NEXT
WEEK WILL BE TALKING ABOUT
HEPATITIS E.
JUST ONE — IT'S NOT ON.
HELLO?
OKAY.
SO ONE OF OUR SPEAKERS NEXT
WEEK, HARVEY ALTER, FROM THE
CLINICAL CENTER, WON, I THINK
IT'S THE MOST PRESTIGIOUS AWARD
GIVEN IN CANADA, THE GARDNER
AWARD.
THIS IS REALLY A BIG DEAL.
HARVEY IS NOT ONE FOR WORDS BUT
THIS IS SOMETHING SPECIAL.
NEXT WEEK HE'S GOING TO TALK
ABOUT A VIRUS THAT MANY OF YOU
MAY NOT KNOW ANYTHING ABOUT,
IT'S SORT OF NEW ON THE HORIZON
TO SOME EXTENT, THAT'S HEPATITIS
E AND.
THE OTHER SPEAKER IS JAKELY WHO
WILL TALK ABOUT SOME OF THE
OTHER ADVANCES IN SOME OF THE
OTHER HEPATITIS VIRUSES.
OKAY.
FOR ANYTHING SAKE, ANYBODY IN
THE AUDIENCE KNOWS THE
POLITICIAN OR SENATOR WHO USED
THIS TERM THE GOLDEN FLEECE AND
GAVE AWARDS EACH YEAR?
OKAY.
SO SENATOR PROXMEYER 20 SOME
YEARS AGO WENT THROUGH NIH
GRANTS AND LOOK THE AT THE
TITLES OF THE GRANTS AND SAID
SOME OF THESE ARE RIDICULOUS.
WHAT ARE YOU STUDYING OR
ANYTHING ELSE.
AND HE MADE A BIG FUSS AND IT'S
THE SAME THING THAT GOES ON
TODAY.
THERE ARE POLITICIANS WHO LOOK
AT THE TITLES OF NIH GRANTS, AND
MOST OF THEM HAVE APPARENTLY
VERY LITTLE APPRECIATION OF
WHERE TRULY BASIC BIOLOGY LAYS
THE FOUNDATION FOR MEDICINE AND
FOR HUMAN HEALTH.
AND OF COURSE THAT'S THE PURPOSE
OF THIS COURSE, THE BROOKLYN
BRIDGE SORT OF BRIDGING SCIENCE,
MEDICINE AND SO FORTH.
SO IT'S INTERESTING THAT IN
READING UP A LITTLE BIT ABOUT
THE HISTORY OF STUDIES OF
CHROMOSOME X, I CAME UPON A
GOLDEN FLEECE STORY WHICH I'D
LIKE TO VERY BRIEFLY SHARE WITH
YOU.
A GENTLEMAN NAMED HENKING IN
1890 DISCOVERED BY STAINING
REACTIONS IN THE TESTES OF A
BUG, OF THE FIREBUG.
IT'S NOT A FIREFLY.
HE OBSERVED BY STAINING THERE
WAS A CHROMOSOME WHICH DID NOT
DIVIDE DURING MITOSIS.
AND HE DIDN'T KNOW WHAT IT WAS,
SO HE CALLED IT LIKE THE X
FACTOR.
HE DIDN'T KNOW WHETHER IT WAS A
CHROMOSOME OR NOT.
CHROMOSOME MERELY MEANS A BODY
THAT STAINS.
WELL LATER IT WAS DISCOVERED
THAT INDEED IT IS A CHROMOSOME.
SO X STOOD FOR THE UNKNOWN.
AND THEN IN LATER YEARS, Y
FOLLOWED X.
THERE WAS NOTHING MYSTERIOUS
ABOUT THAT.
NOW, IN SUBSEQUENT YEARS IN THE
1960'S, MANY YEARS LATER, CAROL
WILLIAMS AT HARVARD WANTED TO
REPRODUCE SOME OF THE
EXPERIMENTS THAT HENKING HAD
DONE IN THE 1890'S.
THEY ACTUALLY GOT SOME OF THE
FIRE BUG DESCENDANTS AND WHATNOT
USED IN THOSE STUDIES.
TOOK THEM TO CAMBRIDGE,
MASSACHUSETTS TO STUDY THEM.
LO AND BEHOLD THEY DIDN'T BEHAVE
AT ALL LIKE THE ONES DID THAT
WERE BACK IN EUROPE.
IN FACT AT HARVARD, THEY DIDN'T
DIVIDE.
SO, THERE WAS A BIG SEARCH AS TO
WHY.
THEY FINALLY DISCOVERED IT WAS
THE ABSORB ENT PAPER ON WHICH
THESE BUGS WERE PUT.
THAT CAME FROM PULP AND PULP
CAME FROM TREES AND THERE WAS
CHEMICALS IN IT.
FINALLY THE BOTTOM LINE OF THE
STORY WAS WHAT CAROL WILLIAMS
DISCOVERED WAS THE FIRST
PHEROMONE-LIKE SUBSTANCE THAT
INFLUENCED THE, IN THIS CASE,
THE SEXUALITY OF THE FIREBUG.
NOW WILLIAMS WAS ONE OF THE
TARGETS OF SENATOR PROXMEYER WHO
KEPT CRITICIZING HIM, WHAT ARE
YOU DOING THESE RIDICULOUS
DISCOVERIES FOR.
THIS WAS ALMOST REALLY THE FIRST
GROWTH FACTOR AS WELL AS THE
PHEROMONE WAS DISCOVERED.
I THINK IT'S A PRETTY DRAMATIC
EXAMPLE WHERE THINGS, HOW WE
LEARN WHERE INFORMATION COMES
FROM.
CAN YOU FLIP THAT ONE.
YES.
SO TODAY, WE'RE VERY FORTUNATE
IN HAVING TWO NIH COLLEAGUES WHO
ARE GOING TO TALK TO US ABOUT
THE X CHROMOSOME.
MALES HAVE ONE, FEMALES HAVE TWO
AND THE AMAZING THING IS ONE OF
THEM COMES FROM THE MOTHER BUT
THE SECOND IS FROM THE FATHER
WHO INDIRECTLY GETS THE MOTHER
FROM THE PATERNAL GRANDFATHER.
SO I TOLD YOU X IS UNKNOWN.
SO X AS A CHROMOSOME CONTAINS
ALMOST 2000 GENES AND ONE X IS
INACTIVATED IN FEMALES WHICH
WE'RE GOING TO HEAR A GREAT DEAL
ABOUT.
WHEN YOU THINK ABOUT IT, AT
LEAST WHEN I THINK ABOUT IT,
SEXUALITY SEPARATES MALES,
FEMALES, IT'S A MAGIC EVENT OF
BIOLOGY THAT'S LENDING ITSELF
MORE AND MORE TO UNDERSTANDING
ATOM MOLECULAR AND CELLULAR
LEVEL.
AND ITS OTHER COMPLEXITY MAKES
IT AMAZING TO REALIZE THAT
THINGS TURN OUT AS WELL AS THEY
DID MOST OF THE TIME.
QUITE REMARKABLE.
BUT WHAT WOULD HAPPEN IF IT
DIDN'T TURN OUT THAT WAY, IF FOR
EXAMPLE THE MALE HAD RETAINED
THE X AND HAD AN XXY.
OR MAYBE MULTIPLE X'S.
WHAT DOES THAT DO TO AN
INDIVIDUAL.
DOES IT PRODUCE A DISEASE, DOES
IT COMPENSATE FOR AND WHAT'S THE
PROCESS IN THE, THAT ELIMINATES
THE ONE X IN THE CASE OF THE
MALE.
SO WHAT HAPPENS IN FEMALES IF
THEY HAVE MULTIPLE X'S.
WELL THIS WHOLE COMPLEXITY IS
INCREASINGLY BEING UNDERSTOOD AT
A MUCH MORE FUNDAMENTAL LEVEL,
AND AT THE SAME TIME THE
DISCOVERY OF INDIVIDUALS IN WHOM
THESE, IN WHOM THE CHROMOSOMES
ARE RETAINED, SORT OF DEFINE THE
NORMAL PATHWAYS THAT GIVE RISE
TO PROPER BALANCE.
THAT'S THE SUBJECT OF TODAY'S
DISCUSSION.
SO WE'RE VERY FORTUNATE, AS I
SAID, IN HAVING TWO COLLEAGUES,
AND ALSO VERY GRATEFUL FOR A
YOUNG LADY WHO IS A PRESENT AND
US WITH SOME OF THE PROBLEMS.
OUR FIRST SPEAKER IS VLADIMIR
BAKALOV WHO WAS TRAINED IN
BULGARIA, CAME TO THE NIH IN
1998 TO START AN ENDOCRINE
FELLOWSHIP, AND HE IS A STAFF
CLINICIAN IN THE NICHD, IN THE
DEVELOPMENTAL END CHRONOLOGY
BRANCH.
AND HE'S BEEN VERY ACTIVE AND
PUBLISHED EXTENSIVELY IN
CLINICAL ASPECTS OF THE TURNER'S
SYNDROME WHICH IS WITH A WE'RE
GOING TO BE FOCUSING ON MORE
TODAY.
OUR SECOND SPEAKER IS CAROLYN
BONDY WHO RECEIVED HER MEDICAL
DEGREE FROM BOSTON UNIVERSITY,
TRAINED IN IN BOSTON AND BECAME
UNDER THE ENDROCHRONOLOGY BRANCH
HERE AND HER RESEARCH HAS
FOCUSED IN AN AWE TENT —
ATTEMPT TO ELUCIDATE THE GENE
DOSAGE EFFECTS THAT COBUTE
TO THESE GENDER DIFFERENCES AND
DISEASE SUSCEPTIBILITY.
AS WE'LL LEARN, THERE IS MUCH
DISEASE SUSCEPTIBILITY THAT
EXTENDS JUST BEYOND THE GENERAL
PARAMETER.
SO I GUESS VLADIMIR, ARE YOU
GOING TO SPEAK FIRST.
SO THANK YOU AGAIN.
>> GOOD AFTERNOON.
I WOULD LIKE TO START THE
PRESENTATION ACTUALLY WITH
PRESENTING A YOUNG LADY WITH
TURNER'S SYNDROME.
FOR THOSE OF YOU THAT HAVEN'T
SEEN HOW PEOPLE WITH TURNER'S
SYNDROME LOOKS LIKE.
SO THIS IS HARRIET GOLD.
SHE'S ONE OF THE PARTICIPANTS IN
OUR STUDY.
SHE'S ALSO ACTIVE RESEARCH IN
OUR STUDY.
SHE HAS BEEN HERE FOR OVER THREE
YEARS ACTIVITY HELPING US IN OUR
RESEARCH.
SO HOLLY, HOW ARE YOU.
>> GOOD, THANK YOU.
>> DO YOU HAVE ANY COMPLAINTS.
>> SIT DOWN, HERE'S THE
MICROPHONE.
>> NOT CURRENTLY.
>> YOU FEEL FINE.
>> ABSOLUTELY.
>> WHEN WERE YOU DIAGNOSED WITH
TURNER'S SYNDROME.
>> I WAS DIAGNOSED WITH TURNER'S
SYNDROME AT BIRTH.
>> AT BIRTH.
WHEN DID YOU LEARN ABOUT YOUR
DIAGNOSIS AT WHAT AGE.
>> AT VARIOUS POINTS I WAS TOLD
DIFFERENT ASPECTS OF THE
CONDITION.
AT AGE APPROPRIATE LEVELS.
SO FOR EXAMPLE IN KINDERGARTEN,
YOU'RE SHORT BECAUSE YOU HAVE A
CONDITION CALLED TURNER'S
SYNDROME.
AS I GOT OLDER CERTAIN PARTS
BECAME DIVULGED.
>> WHEN DID YOU DISCOVER THIS
FOR THE FIRST TIME WITH A
MEDICAL PROFESSIONAL.
>> PROBABLY THE MOST SPECIFIC
EXAMPLE WOULD BE AROUND 10 IN
RELATION TO GROWTH HORMONE
THERAPY AND WHETHER I SHOULD
PURSUE GROWTH HORMONE.
BUT A LITTLE BIT OF DISCUSSION
WITH MY PEDIATRICIAN WHEN I WAS
YOUNGER BUT THAT'S WHEN THE REAL
DISCUSSIONS STARTED.
>> BY GETTING THE INFORMATION
ABOUT YOUR CONDITION FROM
PARENTS AND FROM PHYSICIANS, DO
YOU FEEL YOU WERE GIVEN ENOUGH
INFORMATION.
>> I DO.
>> WITH THE WAY THE INFORMATION
WAS GIVEN TO YOU.
>> NO.
IT DIDN'T IMPACT ME NEGATIVELY
CERTAINLY, ONLY POSITIVELY IN
THAT I KNEW AT THAT AGE WHAT WAS
GOING ON.
AND I'M REALLY GLAD THAT I DID
VERSUS NOT KNOWING.
>> OKAY.
AND SO IT GRADUALLY GAVE TO
REALIZE THE NATURE OF YOUR
CONDITION.
>> YES.
>> WHAT ASPECT OF YOUR CONDITION
WOULD YOU SAY HAD KIND OF MOST
PROFOUND EFFECT IN YOUR LIFE OR
ANY KIND OF PERCEPTION OF
YOURSELF.
>> THAT'S A GOOD ONE.
PROBABLY THE HEART CONDITION IN
TERMS OF [INDISCERNIBLE] AND
SOME OF THE PUBITAL ISSUES IN
TERMS OF THE SOCIAL.
I'M NOT SURE IF THAT WOULD BE
DISCUSSED ALSO.
>> DO YOU FEEL THAT THROUGHOUT
YOUR LIFE AS YOU WERE GROWING AS
A YOUNG GIRL AND LATER AS A
YOUNG LADY, DID YOU FEEL ANY
SORT OF DISCRIMINATION REGARDING
YOUR GENDER.
>> NO.
>> YOUR HEIGHT, ANYTHING LIKE.
>> NO, NOTHING MORE THAN LITTLE
KIDS ON THE PLAYGROUND SHOWING
YOU KNOW YOUR SHORT.
MOST KIDS GET SOMETHING LIKE
THAT.
>> DID YOU HAVE ANY SPECIFIC
DIFFICULTIES IN YOUR LIFE SO FAR
THAT YOU CAN KIND OF RELATE TO
THE TURNER'S SYNDROME.
>> SOME OF THE [INDISCERNIBLE] I
DO WANT TO GO INTO THE MEDICAL
FIELD.
SO THAT'S SORT OF DIFFICULT FOR
ME GIVING THE LEARNING ISSUES.
>> OKAY.
AND HAVE YOU GOT ANY KIND OF
HELP FROM SUPPORT GROUPS OR
SOCIETY.
>> ABSOLUTELY.
OBVIOUSLY THE NIH STUDY WOULD BE
THE MORE IMPORTANT ONE.
>> WOULD YOU KIND OF SHARE WITH
THE AUDIENCE SOME OF YOUR
MEDICAL PROBLEMS THAT YOU WOULD
KIND OF RELATE TO TURNER'S
SYNDROME.
>> I HAVE A BICUSPID AORTIC
VALVE SO I NEED TO GET REGULAR
CHECK UPS.
SLIGHTLY ENLARGED AORTA RELATED
TO THAT.
THAT'S A CONGENITAL CONDITION
THAT'S RELATED TO TURNER'S
SYNDROME.
THYROID CONDITION,
HYPOTHYROIDISM AS YOU NOTICED
HYBRIDITIS IN PARTICULAR.
>> YOU FEEL PERFECTLY OKAY RIGHT
NOW.
>> ABSOLUTELY.
>> ALL RIGHT.
SO I WOULD LIKE JUST BRIEFLY TO
SHOW YOU SOME OF THE FEATURES
THAT WE WILL LATER PRESENT
DURING MY TALK.
SO IF YOU DON'T MINDS YOU CAN
STAND.
ONCE I FINISH.
NOW ONE OF THE MAJOR FEATURES
YOU CAN SEE IS THE STATURE.
SHE'S NOT TYPICAL, SHE'S A
LITTLE BIT ON THE SHORTER SIDE.
BUT ACTUALLY MOST OF THE OLDER
GENERATION PATIENTS WITH
TURNER'S SYNDROME ARE SHORTER
THAN HER.
ANOTHER FEATURE, EXTERNAL
FEATURE IS THE SO CALLED
[INDISCERNIBLE] ANKLE.
IF YOU DON'T MIND JUST TO TURN
AROUND SO YOU CAN SEE ANOTHER
EXTERNAL FEATURE THAT'S CALLED
WEB NECK.
AND LOWER HAIRLINE AND A LITTLE
BIT LOWER.
SO THESE ARE SOME EXTERNAL
FEATURES THAT YOU CAN SEE.
SO WITH THIS, I CONCLUDE MY
CLINICAL PRESENTATION.
IF YOU HAVE ANY QUESTIONS FOR
HOLLY?
>> [INDISCERNIBLE]
>> I DID.
>> [INDISCERNIBLE]
>> FIVE FEET.
FIVE FEET ON THE DOT.
I TOOK GROWTH HORMONE FOR
APPROXIMATELY FIVE YEARS FROM
ABOUT 10 TO 15.
>> ANY OTHER QUESTIONS?
.
>> [INDISCERNIBLE]
>> ABSOLUTELY.
>> [INDISCERNIBLE]
>> RIGHT NOW I'M CURRENTLY
TAKING SOME PREMEDICAL COURSES
AS PART OF A BACCALAUREATE
PROGRAM AND GETTING MY
APPLICATIONS READY FOR MEDICAL
SCHOOL.
>> [INDISCERNIBLE]
>> I WOULD BE APPROXIMATELY FOUR
EIGHT, FOUR NINE WHICH WOULD BE
AVERAGE TURNER'S SYNDROME.
MY PARENTS ARE AVERAGE.
ABOUT FOUR INCHES.
>> OKAY.
ALL RIGHT, THANK YOU.
AND OF COURSE WE WILL HAVE MORE.
[APPLAUSE]
>> NOW I WILL START WITH KIND OF
CLINICAL INTRODUCTION OF TURNER
SYNDROME AND DR. BONDY WILL
CONTINUE WITH YOUR RESEARCH
ASPECTS.
TURNER SYNDROME AS YOU'RE AWARE
THE GUESS IS A CHROMOSOMAL
DISORDER.
IT IS THE ONLY CHROMOSOMAL
ANOMALY COMPATIBLE WITH LIFE.
SINGLE CASES WHERE INITIALLY
DESCRIBED BY NICHOLAI — IN 1925
IN WHAT WAS THEN SOVIET UNION
AND BY OTTO URLICH IN GERMAN
MEDICAL ESTABLISHMENT STILL USES
FOR TURNER SYNDROME.
IN 1938 HELP REA TURNER IN THE
UNITED STATES PUBLISHED AN
ARTICLE IN THE JOURNAL OF END
CHRONOLOGY ENTITLED SYNDROME OF
INFANTILISM CONGENITAL WEBBED
NECK AND CUBE TUESDAY VALGUS
WHICH HE REALIZED WAS A SYNDROME
IN SEVEN PATIENTS.
IN 1959 CHARLES FORD ACTUALLY
DESCRIBED THE CHROMOSOMAL
ABERRATION ASSOCIATED WITH
TURNER'S SYNDROME.
THERE'S THE X CHROMOSOME
PHENOTYPIC FEMALE.
THE MAJOR CLINICAL FEATURES ARE
SHORT STATURE AND PREMATURE —
OF COURSE THERE ARE OTHER
THINGS, SOME SKELETAL AND
ANOMALIES AND EXTURNAL FEATURES
WHICH YOU ALREADY SAW — VERY
IMPORTANT BECAUSE THEY HAVE
IMPACT ON THE LIFE EXPECTANCY.
OTHER CARDIOVASCULAR PROBLEMS,
OSTEOPOROSIS AND FRACTURES.
AUTOIMMUNE DISEASES, METABOLIC
ABNORMALITIES, HEARING LOSS,
SOME CONGENITAL KIDNEY PROBLEMS,
LIVER NORMALITIES AND SOMETHING
I WANT TO STRESS IS NORMAL
INTELLIGENCE THAT YOU SAW.
USUALLY WHEN PEOPLE HEAR A
SYNDROME THEY SO IS YACHT IT
WITH DOWN SYNDROME BUT TURNER'S
SYNDROME IS WITH NORMAL
INTELLIGENCE.
A LITTLE BIT ABOUT THE ORIGIN OF
THIS SYNDROME.
AS YOU CAN SEE IN NORMAL FEMALE,
AND THERE ARE THE HUMAN SPECIES
HAVE FOUR TO SIX CHROMOSOMES —
AND THE FEMALE HAVE TWO
CHROMOSOMES WHICH ARE X
CHROMOSOME AND THE NORMAL MALE
HAS ONE OF THE X CHROMOSOME IS
X, THE OTHER IS Y.
THE TYPICAL CASE OF TURNER'S
SYNDROME WILL HAVE 45
CHROMOSOMES.
AGAIN THE NORMAL 44 AUTO SOME
AND ONE X CHROMOSOME.
SO EITHER X OR Y CHROMOSOME IS
MISSING.
SOMETIMES ONLY PART OF THE
SECOND CHROMOSOME CAN BE MISSING
SO THERE'S ALWAYS ONE NORMAL
CHROMOSOME AND A SECOND
FRAGMENTED X OR Y CHROMOSOME.
AND HERE, I'M SORRY, I HAVE
LISTED SEVERAL OF THE MORE
COMMON AND MORE TYPICAL
STEREOTYPES THAT ARE ASSOCIATED
WITH TURNER SYNDROME.
HOW THIS HAPPENED, USUALLY THERE
IS NON-DISJUNCTION DURING THE
GAM TOE GENESIS.
AND THEN SOME OF THE GAMETES
REMAIN WITHOUT ANY SEX
CHROMOSOME AND THEN IF THIS IS A
SPERM OR AN EGG THEN THEY MEET
THE OPPOSITE GAMETE.
THERE IS ONE SEX CHROMOSOME
LESS.
AND THIS GIVES THE STEREOTYPE OF
45X IN ALL THE CELLS.
HOWEVER THIS ME HAPPEN DURING
MITOSIS ONCE THE EMBRYO IS
FORMED AS A GIRL OR A BOY, AND
THEN PART OF THE CELLS WILL BE
45X, PART OF THE CELLS WILL BE
NORMAL FEMALE STEREOTYPES, FOUR
NORMAL MALE.
IN ANY CASE, THIS WILL END UP AS
TURNER SYNDROME INDIVIDUAL.
IN ANOTHER CASE, THERE WILL BE
JUST WRONG SEPARATION.
INSTEAD OF LONGITUDINALLY, THE X
CHROMOSOME CAN SEPARATE IN A
TRANSVERSE WAY.
THE SHORT ARMS WILL GET TOGETHER
AND THE TWO LONG ARMS WILL GET
TOGETHER AND THAT WILL BE
CALLED — CHROMOSOME.
SO THEN THERE WILL BE THIS
STEREOTYPE WHICH IS CALLED
CHROMOSOME XQ.
THEN THE WHOLE — MISSING WHICH
IS CALLED — AND THE STEREOTYPE
LOOKS LIKE THIS.
THE LONG ARM CAN BE MISSING AND
THE STEREOTYPE CAN DO THIS.
THE BOTTOM LINE IS ALWAYS ONE
NORMAL X CHROMOSOME AND A SECOND
EITHER POSSIBLY MISSING OR
FRAGMENTED CHROMOSOME.
HERE'S THE CONCEPT OF MOSAICISM.
SOME OF THE CELLS WOULD END UP
BEING NORMAL.
THE X AND EVERYTHING WILL BE
NORMAL.
THIS IS A LOWER LEVEL OF
MOSAICISM, PART OF THE CELLS IS
NORMAL AND THIS IS HIGH LEVEL
WHERE MOST — 5X AND THERE ARE A
FEW NORMAL CELLS.
NOW, WHAT IS THE EPIDEMIOLOGY OF
THIS SYNDROME?
ONE IN 200 FEMALE CONCEPTS
USUALLY END UP WITH STEREOTYPE
OF TURNER SYNDROME — LOST
DURING PREGNANCY AND THEN YOU
HAVE ONE IN 2,500 FEMALE BIRTHS.
THIS IS A SPORADIC EVENT.
THERE IS NO ASSOCIATION WITH THE
PARENTAL AGE AND ALSO THERE'S
NOT ANY RACE OR ETHNICITY FOR
DIRECTION.
AND WE CAN ESTIMATE THAT THERE
IS APPROXIMATELY 60,000 WOMEN
WITH TURNER SYNDROME IN THE
UNITED STATES.
SO IT QUALIFIES AS A RARE
DISEASE BECAUSE THE DEFINITION
OF A RARE DISEASE FOR THE UNITED
STATES IS LESS THAN 200,000.
RARE CONDITION I WOULD SAY.
AND A LOT OF, ACCORDING TO A
STUDY IN DENMARK STILL ONLY PART
OF THE PEOPLE ARE IDENTIFIED
WITH TURNER SYNDROME IS GETTING
BETTER WITH YEARS BUT AT LEAST
ONE THIRD ARE NOT DIAGNOSED.
NOW, OUR STUDIES IN 2001
INITIATED BY DR. BONDY.
UNTIL NOW WE HAVE SEEN OUR 455
PATIENTS AGES 7-70.
AND WITH A WE ARE DOING IS
COMPREHENSIVE METABOLIC
CARDIOVASCULAR PSYCHOLOGICAL
ITERATION.
OVER 160 PATIENTS WE HAVE
ADMITTED SEVERAL TIMES AS A
STUDY.
THIS STUDY HAS TWO MAJOR GOALS.
ONE WAS CLINICAL TO STUDY THE
MEDICAL NEEDS OF WOMAN WITH
TURNER SYNDROME AND GOT METHODS
FOR EARLY DIAGNOSIS AND
PROPHYLAXIS THAT INCREASE THE
QUALITY OF LIFE AND LIFE
EXPECTANCY OF THESE PATIENTS.
AND OF COURSE THERE WAS A
SCIENTIFIC GOAL TO STUDY
PRINCIPLES OF X CHROMOSOME
FUNCTION IN A NATURAL — HERE'S
THE AGE DISTRIBUTION OF THE
PATIENTS.
AS YOU CAN SEE, THE MAJORITY ARE
OUTPATIENTS BECAUSE THE FOCUS OF
OUR NOT WHAT HAPPENS AT THE
HOSPITAL SYNDROME.
FOR THE DIAGNOSIS THE MOST
IMPORTANT THING IS THE CARE OH
TYPE.
ALL THE 22 PAIRS OF CHROMOSOME.
THIS TOGETHER WITH THE MOSAIC
CONTAINING NORMAL FEMALE
KARYOTYPE IS FOUND IN 65% OF
INDIVIDUALS IN TURNER SYNDROME
AND OTHER X CHROMOSOME OR Y
CHROMOSOME — ARE FOUND IN 35%.
NOW, IF YOU LOOK AT THE AGE OF
DIAGNOSIS, YOU WILL SEE THAT
LIKE IN OUR PATIENT, A LOT OF
THEM ARE DIAGNOSED ABOUT 20% ARE
DIAGNOSED WITH — USUALLY WITH
THE MOST PRONOUNCED PHENOTYPES.
BUT THEN DURING CHILDHOOD FEW
ARE DIAGNOSED.
AND THEN AROUND THE AGE OF
PUBERTY, THERE IS ANOTHER PEAK
OF DIAGNOSIS.
SO APPROXIMATELY HALF OF THE
PATIENTS DIAGNOSED BY THE AGE OF
13 AND 88% BY THE AGE OF 20.
STRANGELY ENOUGH SOME ARE
DIAGNOSED MUCH LATER IN LIFE FOR
VARIOUS REASONS.
NOW, ONE OF THE CARDINAL
SYMPTOMS ACTUALLY I WOULD SAY
MOST, IF NOT EVERYBODY WILL HAVE
IT, IS THE SHORT STATURE.
AND THE SHORT STATURE IN THIS
CONDITION IS DUE TO — GENE
SUFFICIENCY.
THIS GENE IS LOCATED AT THE
SHORT ARM OF THE X CHROMOSOME
AND THERE'S ANALOGUE IN THE Y
CHROMOSOME.
SO YOU NEED TWO COPIES OF THIS
TO ATTAIN YOUR ATTENTION.
IF YOU HAVE ONLY ONE COPY, THEN
YOU REMAIN RELATIVELY SHORT.
IF YOU HAVE MORE THAN TWO COPIES
LIKE — SYNDROME, FOR EXAMPLE,
WHERE YOU HAVE MORE THAN ONE
AXIOM, YOU ARE TALLER.
SO OVER 95% WILL HAVE SHORT
STATURE, THAT MEANS HIGHER THAN
THE 5 PERCENTILE BUT IF YOU LOOK
AT THE SO-CALLED HIGH DEFICIT.
WHAT IS HIGH DEFICIT.
IT'S THE PREDICTED HIGH
CALCULATED FROM THE PARENTAL
HEIGHT MINUS THE ACTUAL HEIGHT.
IN THE TYPICAL DEFICIT IT'S
APPROXIMATELY 20% A METER.
NOW WHEN YOU LOOK HERE AT THE
CURVE THIS IS THE NORMAL FEMALE
AND THIS IS A WOMAN WITH TURNER
SYNDROME.
YOU CAN SEE THAT DURING THE
EARLY CHILDHOOD BOTH CURVES —
AND THAT'S WHY IT'S NOT UNUSUAL
DIAGNOSIS TO BE MISSED DURING
EARLY CHILDHOOD BECAUSE THE
PHYSICIAN WILL MEASURE THE CHILD
AND WE'LL SEE THIS IS WITHIN THE
NORMAL LIMITS IN THE WORLD
PERCENTILE BUT STILL NORMAL.
EVERYBODY IS DIAGNOSED AROUND
THE AGE OF PUBERTY BECAUSE THERE
IS NO GROWTH SPURT AND THEN HERE
IS THE MOST PRONOUNCED
DIFFERENCE BETWEEN THE DEVELOPED
CHILD.
THIS IS A GROWTH CHART FOR THE
INDIVIDUAL THAT — SO THAT WILL
END UP AROUND 145 CENTIMETERS ON
AVERAGE.
WHICH IS I DON'T KNOW, LIKE FOUR
FEET NINE OR TEN, SOMETHING LIKE
THAT.
HOW DO WE MANAGE THIS GROWTH
DEFICIT?
WELL, THIS IS BY RECOMBINANT
GROWTH HORMONE, DAILY
INJECTIONS.
AND USUALLY THE CHEAPER STARTS
WHEN THE GROWTH AREA'S EVIDENCE.
AND THE EXPECTED HIGH GAIN FROM
THE THERAPY IS FIVE TO TEN
CENTIMETERS AND ON AVERAGE IT'S
7.5 CENTIMETERS AND IT'S FOR
APPROXIMATELY FIVE OR SIX YEARS
THERAPY.
SO WHAT PREDICTS GOOD RESULTS?
EARLY STARTS AND LONGER DURATION
OF THERAPY.
OF COURSE IF YOU HAVE TALL
PARENTS AND RELATIVELY TALL AT
START OF THERAPY IT HELPS.
OF COURSE THERE ARE SOME
ATTEMPTS TO SHIFT THE TREATMENT
OF GROWTH POTENTIALLY AS YOUNG
AS 12 YEARS OF AGE.
SO HERE'S ONE STUDY WHERE THE
TREATMENT — PER DAY GROWTH
HORMONE WAS STARTED AT AVERAGE
AGE OF 2 YEARS BASICALLY.
AND YOU CAN SEE THAT THOSE THAT
ARE GETTING GROWTH HORMONE
GRADUALLY GETTING IN THE NORMAL
RANGE OF HEIGHT COMPARED TO
CHILDREN THAT AGE.
THOSE THAT WERE NOT TREATED WERE
GRADUALLY FALLING OFF FURTHER
DOWN AND DOWN.
NOW, THE OTHER CARDINAL IS
PREMATURE OVARIAN FAILURE.
AS YOU ALREADY KNOW, THESE
PATIENTS HAVE LIMITED EXTERNAL
FEMALE GENITALS — USUALLY ES
INFANT I'LL BUT UNDER THE
INFLUENCE — DEVELOPING TO
COMPLETELY NORMAL.
THE OVARIES AT BIRTH HAVE
VARIOUS AMOUNTS OF — BUT
SMALLER NUMBER THAN 46XX PATH.
AND VERY EARLY IN LIFE A LOT OF
THESE FOLLICLES THAT CONTAIN ALL
SIDES ARE LOST SO AROUND THE
TIME OF PUBERTY, THEY END UP
WITH SO-CALLED — SO OVER 70%
WOULD NEVER DEVELOP PUBERTY.
LESS THAN 50% WILL HAVE SOME
EVIDENCE OF PUBERTY.
FOR EXAMPLE, BREAST DEVELOPMENT.
APPROXIMATELY 15% WOULD
EXPERIENCE BUT LESS THAN 5% JUST
EXCEPTIONAL WILL REMAIN
MENSTRUATING ABOUT LIFE AND
HAVING CHILDREN.
OVER 5% WILL NEED HORMONE
THERAPY TO DEVELOP AND MAINTAIN
FEMININITY — AND OTHER EVENTS
OF HE IS GEN THERAPY.
THIS REPLACEMENT THERAPY
CONSISTS OF ESTROGEN AND
PROGESTERONE.
COULD BE EITHER OF THE
NATURALIST DIAL PROGESTERONE OR
OTHER SYNTHETIC EQUIVALENCE.
THE USUAL PUBERTY INDUCTION,
THOSE THAT DO NOT DEVELOP
SPONTANEOUS PUBERTY AT THE AGE
OF 12 AND THE HORMONAL
REPLACEMENT THERAPY SHOULD
CONTINUE UNTIL AGE 45-50.
OF COURSE THERE ARE A LOT OF
ISSUES THAT SOME OF THESE
PATIENTS WANT TO DISCUSS.
AND THIS IS ONLY LESS THAN 5%
WHO KEPT SPONTANEOUS PREGNANCY.
SO THE MOST VIABLE AT THIS POINT
OPTION FOR THE REST REMAINS THE
IV TECHNIQUES WITH — AND THERE
ARE SOME NEW RESEARCH DONE IN —
IF THERE ARE ANY AT A VERY YOUNG
AGE IN TRYING TO FREEZE THIS AND
USE THEM LATER IN LIFE.
OF COURSE ADOPTION REMAINS
ALWAYS A POSSIBILITY.
NOW HOW SOME OF THE EXTERNAL
FEATURES COME.
THIS IS FEATURES WITH TURNER
SYNDROME WITH MASSIVE
LYMPHEDEMA.
AS YOU CAN SEE INSULATE IN LIFE
GIVES THIS WEB NECK, NECK
WEBBING THE PULLING DOWN OF THE
EARS LOW TO THE HAIRLINE.
ALSO PART OF THE EYES ARE DOWN
SIZING.
THERE'S SOME PARTS OF THE HANDS
AND FEET IN SOME PATIENTS HYPER
CONVEX AND UP TURNED FAILS.
THESE ARE CONSEQUENCES OF THIS
TREATMENT IN LYMPHEDEMA.
SOME OF THE EXTERNAL FEATURES
LIKE THIS CUBE TUESDAY THAT WE
DEMONSTRATED RELATIVELY SHORT
NECK HIGH ARCH, SHORT MET
CARPALS AND METATARSALS FORMED
THESE SHIELD CHESTS.
ALL OF THESE ARE TO SUCH AN
EXTENT THAT GIVES ALSO THE SHORT
STATURE.
AND THERE ARE SOME OTHER
INTERESTING THINGS A LOT OF THEM
HAVE — UNEXPLAIN WHY.
NOW THESE EXTERNAL KNEES AND
THIS MAJOR FEATURES SO FAR LIKE
THE SHORT STATURE DON'T HAVE ANY
KIND OF MAJOR IMPACTS ON THE
HEALTH AND LIFE EXPECTANCY OF
THESE PATIENTS.
BUT THERE IS AT THIS POINT
PREMATURE — WHICH IS FOUR TIMES
INCREASED AND MAINLY IT IS DUE
TO COMPLICATIONS OF CONGENITAL
HEART DISEASE EXTENDED HEART
DISEASE AND METABOLIC
ABNORMALITIES MAINLY DIABETES.
IT WAS ONE OF THE MAJOR FOCUSES
OF OUR STUDY.
SO EVERY NEWLY DIAGNOSED
MEASURES WITH TURNER SYNDROME
NEEDS COMPREHENSIVE CARD SPRAK
SCREENING.
IN WOMEN THAT HAVING DIAGNOSED
AS CHILDREN WHEN THEY FOUND
ADULT CARE PHYSICIANS SHOULD BE
RELATED FOR CARDIOVASCULAR
PROBLEMS.
THE CARDIOVASCULAR COMPLICATION
ACTUALLY IS THE SHORT THING OF
THE LIFE EXPECTANCY IS AORTIC
DISSECTION IN TURNER SYNDROME.
YOU NEED TO SEE IN THE AGE WHEN
THIS HAPPENS WITH TURNER
SYNDROME IS VERY LOW.
TURNER SYNDROME AORTIC
DISSECTIONS ARE NOT ONLY HIGH IN
PREVALENCE BUT THEY HAPPEN AT
YOUNG AGE.
AND THEY AFFECT THE ASCENDING
AORTA.
IN THE POPULATION, IT AFFECTS
MAINLY THE DESCENDING AORTA IN
OLD AGE.
NOW HERE'S ONE OF THE MORE
COMMON ACTUALLY THE MOST COMMON
CONGENITAL ANOMALY IN TURNER
SYNDROME THAT'S CALLED BICUSPID
AORTIC VALVE.
THIS IS THE LEFT VENTRICLE, HERE
THE LEFT ATRIUM.
THE BLOOD COMES RIGHT THROUGH
THE MICRO VALVE AND IS PUSHED
OUT THROUGH THE AORTIC VALVE
INTO THE AORTA.
NOW IF YOU LOOK AT THE SECTION
HERE THROUGH THE AORTIC VALVE
THAT'S HOW THE NORMAL AORTIC
VALVE LOOKS LIKE WITH THREE
REFLEX.
HOWEVER TURNER SYNDROM WITH THIS
REFLEX COMPLETELY OR PARTIALLY
GIVING THE SO-CALLED BICUSPID AS
OPPOSED TO — AND WHEN YOU LOOK
AT THE IMAGE IN THE MRI, YOU CAN
SEE WHEN THIS VALVE OPENS, THE
BLOOD FLOW LOOKS LIKE A TRIANGLE
DURING THIS — AND HERE IT LOOKS
LIKE A FISH MOUTH.
THE DIAGNOSIS POSSIBLE WITH THE
CARDIAC MRI.
CARDIAC MRI IS IMPORTANT FOR
DISCOVERING OTHER PROBLEMS IN
THE AORTIC ARCH.
ANOTHER TYPICAL COMPLICATION
WITH TURNER SYNDROME CALLED —
YOU CAN SEE THIS NARROWING.
THIS IS HOW A NORMAL AORTIC
ATTACK LOOK LIKE.
THIS NARROWING ALSO IF YOU LOOK
AT EXTENDING THE AORTA IT'S IN
THIS PART IT'S DILATED COMPARED
TO THIS ONE.
THIS IS TYPICAL FOR TURNER
SYNDROME.
SO THE MRI SCREENING THAT WAS
INITIATED HERE AT NIH ACTUALLY
TURNS AND VERY MUCH ADOPTED INTO
THIS PRACTICE.
WE HAVE SCREENED THE — WITH
TURNER SYNDROME.
AND 50% WE FOUND SIGNIFICANT
CARDIOVASCULAR ABNORMALITIES.
THE MOST COMMON AS WE MENTION IS
BICUSPID AORTIC VALVE.
WE HAVE APPROXIMATELY THAT MUCH
OF THE DESCENDING AORTA.
10% VEX TREMELY LARGE AORTAS AND
THEN AFTER 15% WERE FOUND
COEFFICIENT AND IN 12% PARTIAL
NORMAL VENOUS REPAIR.
ALL OF THESE THINGS, THE
DILATION AND THE ANEURISM WERE
DIAGNOSED WHEN WE ADJUST FOR THE
SMALL SIZE OF THESE WOMEN.
BECAUSE THE DIAMETER OF THE
AORTA ISN'T TOO BIG AND MANY
TRADITIONAL EXPERTS IN THE FIELD
WILL DISMISS IT ALREADY.
BUT WHEN YOU CORRECT IT REALLY
IS HUGE AND CAN BE CALLED
ANEURISM.
SO THE IMPORTANCE OF THE CARDIAC
MRI CANNOT BE UNDER ESTIMATED AT
ALL.
SO IS DIAGNOSIS BUT CLINICALLY
SIGNIFICANT, ANEURISM OF THE
ASCENDING AND SOMETIMES
DESCENDING AORTA CHRONIC
DISSECTION IN ONE PATIENT FOR
EXAMPLE.
A NORMAL — WHICH IS ALSO
IMPORTANT THAT IT WAS ABLE TO
DETECT A NORMAL AORTIC VALVE IN
15% OF THE CASES NOT DIAGNOSED
WITH THE MUCH WIDELY USE —
CALLED ECHO CARDIOLOGY.
SO THIS IS MUST — TURNER
SYNDROME.
IF YOU HAVE A NORMAL AORTIC
VALVE, IF YOU HAVE HYPERTENSION,
IS THE ASCENDING AORTA IS MORE
THAN 3.5 CENTIMETER AND THE
AORTIC SIZE INDEX SO THIS
NORMALIZE BY BODY SURFACE AREA.
AND OF COURSE PREGNANCY IS
EXTREMELY RISK FACTOR FOR BIG
RISK FACTOR FOR ALL THE
COMPLICATION AND TURNER
SYNDROME.
NOW, THE OTHER ASPECT IS
OSTEOPOROSIS AND FRACTURE.
THERE'S THIS LOW — WAS BY
DR. TURNER EARLY AND AT LEAST
TWO MECHANISMS CAN CONTRIBUTE TO
THIS EITHER ESTROGEN DEFICIENCY
OR CEREBRAL PROBLEM DUE TO THIS
DEFICIENCY.
ONE AT THE NEUROLOGICAL STUDY
FROM DENIAL MARK SHOWS INCREASED
FRACTURES FOR ALL AGES IN TURNER
SYNDROME.
AND WE ARE LOOKING AT THE BOND
SIDES THAT ARE AFFECTED BY
OSTEOPOROSIS.
IDENTITY TYPE OF BONES.
ONE THAT IS SO-CALLED MAINLY —
BONES IN THE SPINE.
THESE SEEM TO BE VERY SENSITIVE
TO ESTROGENS SO IF A WOMAN WITH
TURNER SYNDROME TAKES ESTROGEN
REPLACEMENT THERAPY, THEY TEND
TO HAVE NORMAL LOOKING SPINES.
BUT IF THEY DO NOT TAKE ESTROGEN
THERAPY REGULARLY LIKE IN THIS
37 YEAR OLD WOMAN, THIS IS
COMPRESSION FRACTURE OF THIS
VERTEBRAL BODY.
ALSO, THIS IS A LITTLE BIT
AFFECTED.
SO THE ESTROGEN REPLACEMENT IS
IMPORTANT FOR MAINTAINING —
BONE.
WHAT ABOUT THE LONG BONES OR THE
SO-CALLED MAINLY CORTICAL BONES.
WELL IT LOOKS LIKE IT'S A VERY
SPECIFIC TERMINAL THING.
IF WE MEASURE THE BONE DENSITY
HERE WHERE THE BONE IS MAINLY
CORTICAL, YOU SEE THE PATIENTS
HAVE VERY LOW BONE DENSITY, IT'S
LOWER THAN THE LOWER LIMIT OF
NORMAL.
THIS IS THE KIND OF NORMAL
THAT'S DRIVEN BY AGE.
BUT IN THE SAME PATIENT, IF WE
MEASURE THIS SECTION HERE WHICH
IS MAINLY — BONE BECAUSE THIS
PATIENT WAS TAKING REGULAR
HORMONE REPLACEMENT THERAPY, THE
BONE DENSITY OF THIS PATIENT IS
NORMAL.
AND FOR COMPARISON THIS IS A
WOMAN WITH — BUT TAKES HORMONE
REPLACEMENT THERAPY.
HER CORTICAL BONE IS NORMAL AND
HER — BONE IS SLIGHTLY LOW BUT
WITHIN THE NORMAL RANGE.
SO THIS CORTICO DEFECT WAS
SPECIFIC FOR TURNER SYNDROME AND
PROBABLY IS IMPORTANT FOR SOME
OF THE STRUCTURES THAT THEY
SUSTAINED DURING LIFE.
SO THE REPLACEMENT THERAPY IS
THE MAJOR THERAPY FOR THE BONE
HEALTH AND THIS DETERMINATION IS
VERY IMPORTANT AND ALSO EXERCISE
TAKING VITAMIN D AND OF COURSE
THE PATIENTS HAVE BEEN TO
EDUCATED ABOUT THE OSTEOPOROSIS.
IT WAS NOTED THAT THERE ARE A
LOT OF AUTOIMMUNE DISEASES.
THE MAJOR IS THE THYROIDAL
COMMUNITY THAT CAUSES
HYPOTHYROIDISM AND YOU CAN SEE
COMPARED TO THE U.S. POPULATION.
OTHER DISEASES THAT WE FOUND TO
BE MUCH MORE PREVALENT IN TURNER
SYNDROME COMPARED TO THE GENERAL
POPULATION CAUSES DISEASE AS IN
CELIAC DISEASE.
AS YOU CAN SEE OUR PATIENT HAS
THYROID PROBLEM.
SO METABOLIC ABNORMALITIES IN
PREVIEW OF 225 PATIENTS, WE
FOUND THAT THEY WERE RELATIVELY
YOUNG GROUP AVERAGE AGE OF 35
AND NOT EXTREMELY OBESE JUST
OVERWEIGHTED, 12% HAVE ALREADY
BEEN DIAGNOSED WITH TYPE TWO
DIABETES AT THIS AGE.
WE FOUND 30% MORE AND THIS IS
TYPICAL FOR THE POPULATION
EVERYWHERE, HALF OF THE PATIENTS
NOT DIAGNOSED WITH TYPE TWO
DIABETES ALTHOUGH THEY VISIT.
OVERALL THE PREVALENCE OF TYPE
TWO DIABETES IN THIS POPULATION
IS 25% THE SAME RANGE FEMALES IN
THE UNITED STATES HAVE SOMETHING
LIKE 6% EFFECT OF DIABETES.
AND ANOTHER 25% HAVE IMPAIRED —
SO OVERALL 50% HAVE NORMAL
GLUCOSE HOMEOSTASIS.
THEY ALSO TEND TO HAVE HIGH BAD
CHOLESTEROL AND ALSO MORE —
PARTICLES.
THE DIABETES IS SORT OF UNIQUE
BECAUSE IT'S NOT LIKE IN THE
MAJORITY PATIENTS WITH TYPE TWO
DIE BREATHES IS NOT SO IS —
ASSOCIATED WITH INSULIN —
MILDER AND EASIER TO CONTROL.
NOT PHARMACOLOGICAL
INTERVENTIONS ARE HELPFUL
BECAUSE APPARENTLY CANNOT HANDLE
LARGE AMOUNTS OF SUGARS AND
CARBOHYDRATES SO IT SHOULD BE
AVOIDED.
NOW, WHAT ABOUT THE
PSYCHOLOGICAL OUT COMES.
WHEN WE COMPARE OUR POPULATION
WITH THE AVERAGE AND IT WAS DONE
BY — WITH THE AVERAGE FEMALE
POPULATION IN THE UNITED STATES.
SO WE FOUND THAT THEY HAVE MORE
BACHELORS DEGREES MORE ADVANCED
DEGREES THAN THE OUTS POPULATION
AND WERE MUCH MORE EMPLOYED BY
THE AVERAGE U.S. POPULATION.
AND IT'S INTERESTING SIMILAR
FINDINGS FOUND ELSEWHERE.
SO IT'S VERY OPTIMISTIC OUTPUT
FOR THIS POPULATION.
SO IF WE LOOK IN SUMMARY, WHAT
WE HAVE IS HIGH DEFICIT
PREMATURE — SOME OF THE
EXTERNAL FEATURES WHICH ARE
FOUND IN PROBABLY LESS THAN 30%
GLOB ANNUALS, CONGENITAL
CARDIOVASCULAR DEFECTS WOULD
HAVE IMPACT ON THAT.
LONGEVITY OF HYPERTENSION AND
ARTERIOSCLEROSIS.
METABOLIC ABNORMALITIES, HEARING
LOSS THAT I DIDN'T DISCUSS BUT
AS THE AGE, THERE'S A SENSE OF A
HEARING LOSS OF UNCERTAIN
ETIOLOGY ASSOCIATED WITH TURNER
SYNDROME, CONGENERAL ACTUAL
KIDNEY ABNORMALITIES SOMETHING
THAT WE CALL — IS COMMON.
REALLY DOESN'T CAUSE PROBLEMS.
IF THERE IS URINARY
ABNORMALITIES IT'S CORRECTED
SURGICALLY.
30% HAVE NORMAL INTELLIGENCE.
AND IF WE HAVE TO SUMMARIZE THE
MANAGEMENT, THE SHORT STATURE —
ABOUT THE HEART THEY NEED —
CARDIOLOGY CONSULT AND THE
PREVENTION OF THESE THE DURATION
IS NOT CLEAR HOW IT SHOULD BE
DONE BUT WE WANTED TO DO A STUDY
THAT DIDN'T HAPPEN BUT WE FEEL
THAT ANGIOTENSIN — WOULD BE A
GOOD.
THE THYROID IS TREATED WITH —
DEVELOPED HYPOTHYROIDISM HEARING
LOSS THEY SHOULD ALL UNDERGO —
AMPLIFICATION IF NECESSARY.
AND THERE'S NOTHING UNUSUAL
ABOUT THE TREATMENT OF
HYPERTENSION IF IT SHOWS UP, BUT
AGAIN WE PREFERRED EACH GROUP OF
MEDICATION WHICH IS
HYPERTENSION — OSTEOPOROSIS WE
COVERED, THE METABOLIC SCREENING
IS DONE — PROTEIN.
FOR THE LIVER WE STILL DON'T
KNOW MUCH EXCEPT THAT SOMETIMES
THE LIVER TESTS ABNORMAL.
AND FOR CELIAC DISEASE WE SCREEN
BY MEASURING TISSUE SPECIFIC
ANTI-BODIES AND IT WAS
DISCOVERED [INDISCERNIBLE] DIET.
THAT'S THE END OF MY TALK AND OF
COURSE I WOULD LIKE TO TALK
TO — ORGANIZING THIS STUDY AND
ALLOWING ME TO PARTICIPATE IN
THE RESEARCH.
THESE ARE THE PEOPLE IN
DR. BONDY'S LAB.
A LOT OF PATIENTS AND STUDENTS
ANAFF WAS ALSO
INVOLVED IN THE CLINICAL PART OF
THIS TALK.
THANK YOU VERY MUCH.
[APPLAUSE]
>> WE HAVE TIME FOR A FEW BRIEF
QUESTIONS AND THEN WE HAVE TIME
AT THE END.
YES?
>> IS THE MISSING X OR DEFORMED
X USUALLY THE FAULT OF THE
FATHER OR THE MOTHER?
>> WELL, I THINK DR. BONDY MAY
COVER THIS BUT IT'S EITHER
MISSING X OR MISSING Y.
SO IT COULD BE THE FATHER, IT
COULD BE THE MOTHER, YES.
AND THE MORE COMMON IS A LITTLE
BIT MORE MISSING COMES FROM THE
FATHER.
>> OKAY.
YES, SORRY.
>> ARE THERE ANY MECHANISTIC
INCLUDES FOR THE HIGH PREVALENCE
OF IMMUNE DISORDERS?
>> NOT AT THIS POINT.
>> OKAY.
THANK YOU VERY MUCH AND
DR. BONDY.
>> I WAS GOING TO USE THE
POINTER.
CAN YOU SEE THE POINTER USING
THE ARROW.
IT'S DISCONBOB LING DOING THIS
AND TRYING TO LOOK AT YOU TOO.
I WILL DO THIS SO PEOPLE CAN
HAVE VISUALIZATION WHAT I'M
POINTING AT.
IN THIS NEXT HALF HOUR I WANTED
TO GIVE A LITTLE BIT DISCUSSION
AND UPDATE WHAT WE KNOW ABOUT
HUMANS X CHROMOSOMES AND THEIR
CONTRIBUTIONS TO MAJOR GENDER
DIMORPHIC DEVELOPMENT IN A
NORMAL SENSE, COGNITIVE AND
CARDIOVASCULAR.
AND THEN SUSCEPTIBILITY TO
GENDER AND DISEASES.
SOMEONE MENTIONED AUTOIMMUNE IS
ONE BUT WE FOCUSED ON ISCHEMIC
HEART DISEASE.
IT'S REALLY A MAJOR FACT A MAJOR
REALITY NOT VERY CONVENIENT FOR
OUR SCIENTISTS BUT THERE ARE
VERY IMPORTANT DIFFERENCES IN
THE BEHAVIOR OF SIX CHROMOSOMES
COMPARED TO AUTOZOMES BUT THE
MOST GENETIC THEY ARE AND
EXPERIMENT ARE OPTOSOMAL GENES
AND NOT SEX LINKED GENES.
THERE'S BIG DIFFERENCES IN
SPECIES WITH REGARD TO MECHANISM
OF SEX DETERMINATION, DOSAGE
COMPENSATION, CHROMOSOMAL
EFFECTS IS VERY DIFFERENT.
WE DON'T HAVE A GOOD MODEL
EXPERIMENTAL MODEL FOR HUMANS.
AND SO WE'LL TALK A LITTLE BIT
ABOUT DOSAGE COMPENSATION, X
INACTIVATION IN HUMANS, SEX
CHROMOSOME ANOMALIES AND WHAT
THEY TELL US ABOUT GENES THAT
APPARENTLY DO NOT GET X
INACTIVATED AND IF WE HAVE TIME
AT THE END I'LL TALK ABOUT SOME
OF ONOR WORK ON THE IMPORTANT X
CHROMOSOME IMPRINTING.
THIS IS A SCANNING ELECTRON
DUPLICATED X AND Y CHROMOSOME.
WHEN NOTED THE X IS NOT BECAUSE
IT LOOKS LIKE AN X BUT BECAUSE
IT WAS AN UNKNOWN FACTOR THAT
WAS BEHAVING IN A MYSTERIOUS
FASHION MANY DECADES AGO AND THE
Y CAME MUCH SMALLER AND MANY
MORE DIFFICULT TO DISCERN AND
WAS DISCOVERED MUCH LATER.
AND IT WAS DISCOVERED TO BE SEX
DETERMINING IN MY LIFETIME.
NOT ALL THAT ANCIENT HISTORY.
SO THE BIG DIFFERENCE IS SIZE.
SO THE X CHROMOSOME IS THE
NORMAL, SAME SIZE AS THE
AUTOSOME OR A LITTLE BIGGER
WHILE THE Y IS TINY.
SO WHAT'S HAPPENING HERE, AND IN
RECENT YEARS WITH THE EXPLOSION
OF GENOME SEQUENCING WE'VE HAD
AN OPPORTUNITY TO LOOK AT THE
SEQUENCE OF MANY SPECIES.
THERE'S A LOT OF INTEREST IN THE
RESEARCH WORLD IN X CHROMOSOME
AND SOME PEOPLE MAKE THEIR
ENTIRE LIFE SEQUENCING MALE
CHROMOSOMES AND TRYING TO FIGURE
OUT WHAT'S GOING ON WITH IT.
AND I SHOW THIS SLIDE, I'M NOT
GOING TO TRY TO DETERMINE
DIFFERENCES IN THESE SPECIES OR
COMMENT ON COMPLETELY WEIRD AND
VERY DIFFERENT MECHANISMS OF SEX
CHROMOSOME STRUCTURE AND SEX
DETERMINATION.
THIS IS ONLY THE RELATIVELY
MODERATE STUFF.
INSECTS, FRUIT FLIES GET
STRANGER AND STRANGER.
IF EVER WANT TO ARGUE WITH
SOMEBODY ABOUT INTELLIGENT
DESIGN BRING UP MECHANISM OF SEX
DETERMINATION IN CHROMOSOMAL
EFFECTS.
NOBODY DESIGNS THIS.
IT'S COMPLETELY CRAZY.
AND THE THINGS, SO, THE
MECHANISMS FROM DIFFERENT
SPECIES ARE VERY DIFFERENT.
AND EVEN IN OUR FAVORITE MODEL
THE MOUSE, THERE IS A VERY BIG
DIFFERENCE IN SEX CHROMOSOMES.
SO ABOUT THE TIME OF THE
EVOLUTIONARY DIVERGENCE OF
MONITORING A GENE CALLED THE SEX
DETERMINING ON THE Y WAS
APPARENTLY INSERTED ON TO A
PAYER OF AUTOZOMES.
AND THE KANGAROO TYPES AND THE
MAMMALS EVOLVED EVEN MORE
EXTREMELY.
AND YOU SEE THAT THESE
CHROMOSOMES END UP WITH Y
SHRINKAGE RELATIVE TO THE X AND
AUTOZOMES.
AND ALSO YOU HAVE SOME PRETTY
BIG DIFFERENCES IN HUMAN SEX
CHROMOSOMES.
NOW WHY IS THE Y SHRINKING?
AND BECOMING DEGENERATE.
THIS IS A THEORY BUT IT SEEMS
PRETTY REASONABLE TO ME.
THE SEX CHROMOSOMES
DIFFERENTIATED FROM A PAIR OF
AUTOZOMES THAT HAD GENETIC
REGULATION ABOUT A THOUSAND
GENES PERCHROMOSOME.
BOTH GENES WERE EXPRESSED BY
EXPRESS, PA PATERNAL CHROMOSOME
EXPRESSED.
AT SOME POINT IN TIME THIS SRY
GENE A MAMMALIAN MALE SEX CHROME
COMB A MALE SEX DETERMINATION
GENE APPEARS.
THIS SRY TYPE OF GENE.
HERE IT LOOKS LIKE A PURPLE MALE
DETERMINING GENE.
SO IF THESE CHROMOSOMES UNDERGO
THE NORMAL PRACTICE OF PAIRING
AND RECOMBINATION DURING GAMETE
FORMATION, WHAT WILL HAPPEN TO
THE MALE SEX?
IT WILL GET SPREAD BACK
AND FORTH WITH THE ANTAGONISTIC
GENE CAME AND PAIRED WITH THE
SLY GENE.
IT MOVED THE SLY GENE UP AND
DOWN ON THE Y CHROMOSOME.
TRYING TO PREVENT RECOMBINATION
LED TO ANTAGONISTIC
RECOMBINATION BLOCKING ON THE Y
AND TO SOME EXTENT ON THE X BUT
PREVENTED RECOMBINATION.
WHAT HAPPENS WHEN YOU PREVENT
PRERECOMBINATION.
GENERIC DETERIORATION.
SO THEY CALL IT PSEUDO
GENIZATION ON THE Y.
ON THE Y ARE MUTATED AND
FUNCTIONAL AND BUILDS UP A LOT
OF RECOMBINANT DNA AND YOU CAN
LOSE ALL OF THAT REPETITIVE OR
NON-CODING DNA.
YOU'LL END UP WITH A SHRUNKAGE Y
CHROMOSOME THAT HAD GENES ON IT
COMPARED TO ABOUT A THOUSAND ON
THE X CHROMOSOME.
DOES THAT MAKE SENSE?
DO YOU BUY THAT THEORY.
SOME PEOPLE BELIEVE THAT THE Y
IS GOING TO BE EXTENT BECAUSE IT
KEEPS LOSING ITS GENES BECAUSE
IT WON'T, IT CAN'T RECOMBINE AND
THAT SOME DAY — THERE'S A LOT
OF DISCUSSION IN THE CHROMOSOME
BIOLOGY ABOUT WHETHER IT'S
ACTUALLY GOING TO GO EXTINCT OR
WHETHER THERE WILL BE A
PURIFYING, I CAN'T REMEMBER WHAT
IT IS.
IT'S THE Y CHROMOSOME FORMS HAIR
LOOPS AND RECOMBINES THEM.
IT CLEANS UP ITS MUTATIONS IN
THAT WAY BUT WE SHALL SEE.
SO THIS REFLECTS, I JUST MENTION
THAT THE Y CHROMOSOME HAS LOST
MOST OF THE CODING GENES AND X
HAS MORE ABUNDANT GENE.
WE ARRIVED AT A SITUATION WHERE
THE Y IS VERY SMALL VERY FEW
GENES AND ONLY HAVE ONE X WHILE
WOMEN HAVE TWO.
AND MALES HAVE ONE X CHROMOSOME
AND FEMALES HAVE TWO.
FEMALES ARE GOING TO HAVE TWICE
AS MUCH GENE EXPRESSION RELATED
TO THE X CHROMOSOME, BRAIN
DEVELOPMENT IMMUNE SYSTEM
FUNCTION AND SO FORTH.
OR HOW WE'RE GOING TO WORK THAT
OUT.
THIS WAS A THEORETICAL QUESTION
FOR SOME NUMBER OF YEARS AND
THERE ARE DIFFERENT
POSSIBILITIES.
YOU COULD REDUCE THE FEMALE GENE
EXPRESSION BY 50% OR YOU COULD
AMP UP THE MALE FROM HIS SINGLE
X BY TWO-FOLD OR SO.
AND THERE ARE DIFFERENT SPECIES
THAT USE ANY NUMBER OF
VARIATIONS ON THIS THEME.
THE KIND OF INTERESTING THE WAY
THE MAMMAL SYSTEM OF DEALING
WITH THIS CAME ABOUT.
AND MANY OF YOU HAVE HEARD THAT
YOU HAVE TO BE A FEMALE CAT TO
HAVE THREE COLORS, A CALICO COAT
OR TO A HAVE A MOTTLED BLACK
ORANGE AND WHITE COAT LIKE THE
TORTOISE SHELL CAT.
THIS WAS CAUSING INTEREST IN THE
FIELD OF CLASSICAL MEDIC IN THE
1950'S AND 1960'S.
THERE WAS A LOT OF CONVERSATION
ON HOW IT WAS SEGREGATED
ACCORDING TO — AND SAME THING
FOR MICE.
BUT IT'S KIND OF A NICE STORY
FOR CATS.
AND SO THESE GENETICISTS WORKED
OUT THAT THIS COAT COLORED GENE
HAD TO BE ON AN X CHROMOSOME AND
THEREFORE THE MALE HAS ONLY ONE
CHROMOSOME CAN BE EITHER
ORIGINAL OR BLACK.
BUT HE CAN'T HAVE A LOT OF
DIFFERENT X CHROMOSOMES AT LEAST
ACCORDING TO CLASSICAL GENETICS.
HOWEVER, THE FEMALE SHE HAS TWO
X'S AND SHE HAS THEREFORE AN
ORANGE COAT BEGAN POSSIBLY.
HOW DO YOU TURN UP AS A CALICO.
I DON'T KNOW IF MARY LIONS CAME
UP WITH A GOOD HYPOTHESES TO
EXPLAIN IT.
SHE WROTE A BEAUTIFUL PAPER ON
HOW THAT HAPPENED.
SO THE CONCEPT OF RANDOM X
INACTIVATION DURING EMBRYONIC
DEVELOPMENT LEADING TO SCHEMATIC
CELL MOSAIC S FOR TRACING
FEMALES IS THAT CONCEPTS.
SO THAT WAS KIND OF A BEAUTIFUL
DEDUCTION OF A MAJOR GENETIC
FACT JUST LOOKING AT CLASSICAL
GENETICS AND THE CALICO CAT.
AND THEN ALSO MICE THAT HAVE
COAT CODED GENES.
THAT HYPOTHESES WAS NORMALIZED
BY MARY LIONS IN A ONE PAGE IN
1961 WITH CAT AND MICE AND THEIR
COAT COLORED LED HER TO PROPOSE
THAT EXTRA X CHROMOSOME BE IT A
SECOND X OR ANY KIND OF SUPER
NOOMARY NUMBER OF X CHROMOSOMES
HAPPENING DURING ANGIOGENESIS
EXPLAINING THE COAT COLOR IN
MICE AND CATS.
AND THIS FORMED —
HETEROCHROMATIN LUMPED ON THE
NUCLEAR PERIPHERY SHOWN HERE.
OF COURSE THIS USED TO BE USED
AS A FEMALE SEX DETERMINING AND
GENETIC TEST THAT WILL TAKE
EPITHELIAL CELLS.
SO IN MORE RECENT YEARS
MECHANISMS OF X INACTIVATION
HAVE ATTRACTED A LOT OF INTEREST
AND THIS IS A PRETTY WELL
ACCEPTED MAMMALIAN MECHANISM FOR
HOW THIS HAPPENS.
ON THE CHROMOSOME IS AN X
INACTIVATION CENTER AND IT
PRODUCES A NON, A LONG
NON-COATING RNA CALLED THE X
INACTIVATION SPECIFIC TRANSCRIPT
OR XIST AND THAT COATS ONE OF
THE X CHROMOSOMES.
SO IT'S THE ACTS THAT PRODUCES
XIST IS UP AND DOWN AS
ILLUSTRATED HERE.
THIS SOMEHOW IS NOT WELL
UNDERSTOOD AT ALL LEADS TO A
MORE PERMANENT AND INHERITABLE
PATTERN OF X INACTIVATION WHERE
THERE'S METHYLATION WHICH I
GUESS IS THE PINK DOTS.
AND THEN THERE'S MODIFICATION OF
HIS TO MAKE IT UNFRIENDLY — SO
DNA METHYLATION AND THEN
MODIFICATION OF HISTONES TO MOVE
IT TO AN INACTIVE STUDIES.
THAT IS THE CURRENT CONCEPT OF X
INACTIVATION IN MAMMALS.
MOST OF THE WORK HAS BEEN DONE
IN MICE AND A LOT OF THE WORK IN
MICE HAVE BEEN DONE IN EMBRYONIC
STEM CELLS IN MICE.
SO IT'S AN OPEN QUESTION WHETHER
THIS APPLIES TO HUMAN IN THE
NORMAL PROCESS OF ANGIOGENESIS
IN HUMANS.
THERE'S QUITE A BIT OF EVIDENCE
THAT SUGGESTS IT'S NOT THAT
RELEVANT.
IT'S THERE BUT IT'S PRODUCED
FROM BOTH X CHROMOSOMES AND SO
EXACTLY HOW IT WORK IS NOT
CLEAR.
SO SOME OF OUR CRITICAL
OBSERVATIONS NOW WE'VE
ESTABLISHED THAT WE HAVE TO HAVE
X INACTIVATION TO PREVENT
FEMALES FROM HAVING DOUBLE DOSE
OF POTENTIALLY HARMFUL X CHROME
— CHROME SOMES COMPARED
TO FEMALE — PHENOTYPE TO ODD
NUMBERS OF CHROMOSOMES.
THIS IS PRETTY COMMON, ONE IN
500 BOYS HAVE IT.
PHENOTYPICAL MALE BECAUSE HE HAS
THE Y WITH THE SEX DETERMINING
GENE.
AND HE HAS TALL STATURE
BECAUSE HE HAS TWO COPIES, THREE
COPIES.
AND MILD COGNITIVE AND
BEHAVIORAL ISSUES THAT ARE NOT
WELL CHARACTERIZED IN GONADAL
FAILURE YOUR PHENOTYPIC FEMALE,
SHORT STATURE — DOESN'T REALLY
ATTRACT A LOT OF ATTENTION.
AGAIN MILD COGNITIVE INDUSTRIAL
ISSUES.
AND IN THE TRIPLE X PREMATURE
MENOPAUSE.
NOT ABSOLUTE INFERTILITY BUT
PRETTY CHARACTERISTIC PREMATURE
MENOPAUSE.
THAT IS HOW THEY GET PICKED UP
BY GOING TO THE PRODUCTIVE
CLINIC — I'M NOT READY FOR
MENOPAUSE AND THEN THEY DO A
KARYOTYPE.
YOU PROBABLY HEARD ABOUT A SUPER
MALE AN XYY MALE?
THIS IS NOT REALLY A SYNDROME.
THESE ARE NOT SICK PEOPLE.
IT'S VERY VERY SUBTLE
MANIFESTATIONS OF ANY SORT, AND
THEY ARE MALES AND THEY HAVE 12
STATURE.
SO THE SYNDROME WE TALKED MOST
TODAY IS TOUCHER SYNDROME WHERE
A FEMALE HAS A SIJ X MILD
COGNITIVE AND BEHAVIORAL ISSUES
IN SOME SUBJECTS, CONGENITAL
HEART DEFECTS AND EXCESS
CORONARY.
WE SEE THAT THE Y CHROMOSOME
DESPITE THE NUMBER OF X'S YOU
HAVE ARE GOING TO BE MALE AS
LONG AS YOUR SRY GENE IS IN TACT
AND THE — GENES ARE IN TACT AND
THE X AND Y THAT'S ABSOLUTE
NUMBER OF CHROMOSOMES CORRELATES
WITH HEIGHTS POSITIVELY.
THEN WE ALSO SEE THAT EITHER
INCREASED DECREASED X CHROMOSOME
DOSAGE — AND LIKEWISE MOST
INCREASED AND DECREASED X
CHROMOSOME DOSAGE SEEMS TO BE
ASSOCIATED WITH NEWER COGNITIVE
ISSUES.
MILD ISSUES BUT PRETTY
REPRODUCIBLE.
SO WHY ARE SEX CHROMOSOME AN
PLOIDZ SO COMMON.
WITH THE MAMMALIAN DEVELOPMENT
ON THE Y CHROMOSOME THAT
RECOMBINATION WAS SUPPRESSED —
MIXING IT UP EVERY TIME.
WITH RECOMBINATION BEING PRESSED
PAIRING IS RELIABLE.
CHROMOSOMES EVER LOST OR BROKEN.
BASICALLY THE MECHANISM TO
PRESERVE THE MALE DISTINCT FROM
THE FEMALE SEX MAKES IT MORE
LIKELY YOU'RE GOING TO LOSE THAT
CHROMOSOME DURING MEIOTIC —
GENESIS.
HERE IT SHOWS THE X FEMALE EGG
GIVING MICE GONADA GIVING RISE
TO EGG ON THE ONE HAND TWO X'S
AND THE OTHER HAND NO X'S.
THIS CAN GIVE RISE TO, IF IT
GETS A PATERNAL X, A FEMALE
TURNER SYNDROME.
IF IT GETS, IF THE TWO X'S GET A
PATERNAL X YOU GET A FEMALE AND
TRIPLE X SYNDROME.
IF IT GETS A MALE I YOU HAVE
COMBINED FILTERS PERSON.
IF YOU HAVE NO X, NO DICE.
IT'S TOTALLY NON-VIABLE.
BUT THE LIKELIHOOD OF
ANEUPLOIDIES TURNING UP A
SPERMATOCYTE WITH SIX
CHROMOSOMES IS EQUALLY LIKELY.
IT'S NOT THAT MEIOTIC ERRORS ARE
MORE COMMON IN THE FEMALE VERSUS
THE MALE WITH REGARD TO SIX
CHROMOSOMES.
SO GOING BACK TO TURNER SYNDROME
FOR THE X CHROMOSOME ONE OF THE
VERY FIRST QUESTIONS IS IF THE
SECOND X IS COMPLETELY
INACTIVATED ACCORDING TO THE
HYPOTHESES WHY SHOULD THERE BE
THEY PHENOTYPE AT ALL.
WELL THE LEADING MOTS —
HYPOTHESES IS THERE ARE SOME
GENES REPRESENTED ON BOTH X AND
Y BY EXPRESSION TWO DOSES OF
WHICH ARE ESSENTIAL FOR NORMAL
DEVELOPMENT.
AND THE OTHER POSSIBILITY WHICH
WE'VE ALSO BEEN INTERESTED IN IS
THAT SINCE 45XX WOMEN, WE ARE
MOSAICS.
SOME CELLS IS FROM THE FATHER
SOME CELLS ARE FROM THE MOTHER.
SO IF THERE WAS AN IMPRINTING OF
THE PARENTAL X, YOU COULD HAVE A
PHENOTYPE RELATED TO BEING MONO
CHROMIC.
ANYWAY, THE GENES THAT ARE
REPRESENTED IN TWO COPIES HAVE
BEEN CHARACTERIZED IN THE HUMANS
PSEUDO AUTOSOMAL REGIONS AND
THEY'RE LOCATED ON THE TERMINAL
POSURES — PORTIONS OF THE
SHORT
ARM.
THE YELLOW IS A FLUORESCENT
IMMUNOSIGNAL FOR AN ACTIVE
HISTONE FORMULATION SO THERE'S
ACTIVE TRANSCRIPTION HERE AT THE
TIP OF THE P AND OVER HERE IN
THE SHORT ARM PROXIMAL REGION
AND A LITTLE BIT HERE AT THE TIP
OF Q.
AND HERE IS THE ACTIVE X WITH,
YOU KNOW, MUCH OF THE CHROMOSOME
BEING TRANSCRIBED OF Y WITH A
LITTLE BIT OF PINK TERMINAL
ACTIVITY AND PROXIMAL XP
ACTIVITY.
SO THESE REGIONS WERE DISCOVERED
BY FIRST NOTICING THE SEX
CHROMOSOMES DO PAIR DURING
MEIOSIS.
THEY HAVE TO PAIR AT THESE
REGIONS.
IT TURNS OUT ON SEQUENCING AND
THESE REGIONS HAVE BEEN
EXTREMING DIFFICULT TO SEQUENCE.
THEY'RE STILL NOT SEQUENCED TO
ANY SPECIES THAT'S BECAUSE
RECOMBINATION RATE IS
ASTRONOMICAL AND THE MALES KEEP
CHANGING THEIR SEQUENCES AND
IT'S DIFFICULT TO SEQUENCE IN A
STRAIGHTFORWARD MANNER.
IN ANY CASE THESE REGIONS AS
INDICATED BY THIS
IMMUNOFLORESCENCE BY THIS
CARTOON ESCAPE THE PROCESS OF X
ACTIVATION AND THERE'S MUCH
HIGHER RESOLUTION FOR THE
SHOWING KIND OF LIKE A CLOUD X
CHROMOSOME CHROMATIN WITH LITTLE
HAIR-LIKE COMING OUT BUT
SUSTAINS FOR ACTIVE
TRANSCRIPTIONS.
THE MAJORITY OF THE CHROMOSOME
IS HITTING WITH THE CHROMATIN
COATED WITH METHYLATED PROMOTERS
WITH REPRESSIVE HISTONES AND
THERE CAN BE A LITTLE PART OF
THE GENE THAT GETS OUT OF THAT
CHROMATIN HAS A — METHYLATION
AND HAS ADDED TRANSCRIPTION
GOING ON.
SO DR. BAKALOV MENTIONED THE
SHOX.
IT'S IMPORTANT WE CONSIDER ON
HOW THIS GENE WORKS — IT'S BOTH
SENSITIVE ON SEX CHROMOSOMES.
SO THE MORE SEX CHROMOSOMES YOU
HAVE THE TALLER YOU'LL BE UP TO
A POINT AFTER WHICH YOU TIP OVER
AND CAN'T GET ANY TALLER.
BUT THE SHOX CHROMOSOMES ALSO
MAKES YOU SHORT.
THIS WAS DISCOVERED BY STUDYING
PEOPLE WHO HAD POINT MUTATIONS
AND MICRO DELETIONS AND BEING —
FOR STATURE.
IT WASN'T DETERMINED FROM TURNER
SYNDROME BUT IT'S PRETTY
CONCLUSIVE.
THIS GENE IS IMPORTANT BECAUSE
IT SUPPORTS MY CONCERN THERE'S
NOT A LOT OF CONSERVATION OF PAR
1 WHICH IS HUMANS.
THIS IS FROM A WEBSITE PRO GUARD
FIELD WHICH HAS THE GENOME ON IT
AND IT'S THE LATEST VERSION OF
THE CAT X CHROMOSOME SEQUENCE.
THAT'S JUST A REFERENCES AND
THEN THE HOMOLOGOUS BLOCKS ARE
SHOWN DOWN HERE.
THE CLOSEST IS THE DOG AND THE
NEXT CLOSEST IS THE HUMAN.
THE CHIMP AND GORILLA ARE NOT
THAT CLOSE AND THE MOUSE AND THE
RAT HAVE BASICALLY NO
CHROMOSOMAL REGION RELEVANT TO
OURS.
THAT'S A BIG PROBLEM BECAUSE
MOUSE IS OUR COMMON MODEL FOR
THESE THINGS.
SO THE PRESENCE OR ABSENCE OF
PAR ONE DETERMINED THE PHENOTYPE
FOR TURNER SYNDROME.
MICE WHO DON'T HAVE PAR 1 SHOWN
HERE ARE FERTILE, NORMAL SIZED
AND HAVE NORMAL SURVIVAL, BORN
IN THE NORMAL RATIO AND NORMAL
SURVIVAL POSTNATALLY.
IT SEEMS TO HAVE ALMOST NO
EFFECT IN MICE.
IT'S ALSO INTERESTING BECAUSE
THAT MEANS THAT ANEUPLOIDIES PER
SE ISN'T FATAL.
HAVING AN IMBALANCE OF
CHROMOSOME IS NOT ONE SPECIFIC
PROBLEM.
IT SEEMS TO IMPLATE AUTOSOMAL
GENES PRESENT IN THE HUMAN AND
MAYBE IN OTHER SPECIES LIKE THE
CAT WHO HAS THE PHENOTYPE
PRACTICALLY IDENTICAL TO THE
HUMAN.
SO THIS JUST FURTHER, YOU KNOW,
EXPLAINS THE ATTRITION OF PAR 1
IN MICE.
THE PAR 1 GENE THERE IN THE
HUMAN, THERE'S ABOUT 25 GENES,
KNOWN COATED GENES HERE.
THERE'S PROBABLY OTHER
TRANSCRIPTS THAT ARE IMPORTANT
ON COATING RNAs AND SO FORTH.
BUT THE GENES FROM THE MOUSE
HAVE MIGRATED TO OTHER
CHROMOSOMES OR THEY'RE NOT
PRESENT IN THE MOUSE GENOME AT
ALL.
AND IN PARTICULAR, SHOX IS NOT
PRESENTED IN MICE.
THIS IS AN ERROR IN SIMILAR
GENES BUT NOT EXACTLY THE SAME
GENE AND SO THAT EXPLAINS WHY
THEY HAVE MORE PHENOTYPE.
BUT IT'S IMPORTANT TO REMEMBER
THE IMPORTANT GENES ARE
SOMETIMES PRESENT ON HUMANS
CHROMOSOMES BUT NOT WORTH IT IN
THE MOUSE.
WE HAVE MAPPED DELETIONS IN
PEOPLE WITH TURNER SYNDROME TO
SHOW WHERE THE CONGENITAL HEART
DISEASE LOCUS IS, AND WE'VE
SHOWN IT'S ON FROM THE MEDICINAL
PORTION OF THE SHORT ARM XP
TERMINAL AND WE SUSPECT VERY
STRONGLY IT'S A — BUT HAVEN'T
BEEN ABLE TO FURTHER DEFINE IT.
HERE'S ONE WHERE OUR MOST
INFORMATIVE PATIENT HAD A BREAK
HERE AT THIS LOCUS AND THE X
CHROMOSOME FOCUSED ON GENES
TELOMERIC TO THAT AS CANDIDATES.
I'M NOT GOING TO HAVE TIME TO
TALK ABOUT ISCHEMIC HEART
DISEASE, AND SO I WILL JUST END
HERE.
I'LL GET TO MY THANK YOU SLIDE
THANKING MY FELLOWS AND
COLLEAGUES AND THE DIFFERENT
INSTITUTES AT NIH AND THE NIH
CLINICAL STAFF AND ALL THE GIRLS
AND WOMEN AND THEIR FAMILIES
THAT PARTICIPATE IN OUR
PROTOCOL.
THANK YOU.
[APPLAUSE]
>> [INDISCERNIBLE]
>> IN XYY.
BECAUSE THEY DID THE SCREENING
AT HOMES FOR THE RETARDED.
AND SO BECAUSE THEY WERE TAKING
SAMPLES FROM THOSE PEOPLE
WITHOUT IN THE DAYS BEFORE
PATIENT PROTECTIONS CAME IN,
THEY WERE SAMPLING PEOPLE WHO
HAD NO CHOICE.
THEY WERE JUST DOING GENETIC
STUDIES ON THEM.
WHEN THEY DID IT IN A AT HOME
POPULATION IN THE UK — ABOUT
5,000 MALES AND THEY FOUND 2-3%
HAD YXX.
THERE'S NO — TENDENCIES OR
RETARDATION.
X CHROMOSOMES ARE NOT VERY GOOD
FOR YOUR BRAIN BUT XXY DON'T
SEEM TO HURT.
THERE'S A LOT OF EXCELLENT
BRAIN — THE MORE COMMON FORM OF
MENTAL RETARDATION EXPERTS —
THERE'S A LOT OF BRAIN GENES AND
A LOT OF IMMUNE — ON THE X
CHROMOSOMES.
>> YOU MENTIONED HOW X DELETION
SO ZERO Y IS NOT AVAILABLE.
ARE THERE PARTIAL XYs THAT ARE
AVAILABLE.
>> NOT WITHOUT, YOU MEAN
SOMEBODY WITH AN IMPACT NORMAL X
CHROMOSOME.
>> [INDISCERNIBLE]
>> NO.
YOU'RE SAYING A MALE WITH AN X
DELETION.
>> [INDISCERNIBLE]
>> THEY'RE NOT VERY WELL
TOLERATED.
MALES DO NOT TOLERATE X
CHROMOSOME DELETIONS AT ALL WELL
BECAUSE MANY OF THOSE ARE
ESSENTIAL TO THEIR LIFE.
BUT THERE ARE MICRO DELETIONS IN
THE LONG ARM THAT ARE TOLERATED
BUT YOU NEED A PRETTY INTACT X
CHROMOSOME TO SURVIVE, AT LEAST
ONE.
>> SOME GENES FOR THE PERCEPTION
OF COLOR ARE ENCODED ON THE X
CHROMOSOME.
IS THERE A HIGHER PREVALENCE
EXPECTED OF COLOR BLINDNESS IN
TURNER SYNDROME.
>> IT'S THE SAME AS IN THE MALE
POPULATION.
AND ANY EXCELLENT GENE DISEASE
LIKE HEMOPHILIA OR — DEHIGH
DRAWJ FACE DEFICIENCY IS THE
SAME IN THE GENERAL MALE
POPULATION.
>> — OVER SEVEN FEET, FOR THE
MOST PART ARE THEY MULTIPLE Y OR
NORMAL XY THAT HAPPEN TO BE
TALL.
>> THAT'S A VERY GOOD QUESTION.
I DON'T THINK ANYBODY SCREENED
THEM.
BUT ONE POSSIBILITY IS IN SOME
CASES PEOPLE ARE USING
STRATEGIES LIKE — TREATMENT TO
GET PEOPLE TALL DURING THEIR
TEENAGE YEARS.
>> DO WE HAVE AN IDEA FROM ANY
SEQUENCING ON THE X CHROMOSOME
AS TO WHAT THE CLUES ARE ABOUT
THE MECHANISMS FOR PARTICULARLY
THESE CARDIOVASCULAR EFFECTS
LIKE FOR EXAMPLE ONE THOUGHT
WENT THROUGH MY MIND THAT IS THE
COPE APTATION —
>> DOES ANYBODY KNOW — IS THAT
A MALE OR A FEMALE.
>> THE BICUSPID?
>> IT'S A FEMALE PROBABLY.
>> BICUSPID AND CAUCASIAN ARE
ABOUT FIVE TIMES MORE COMMON IN
MEN THAN WOMEN.
SO THAT'S INTRIGUED PEOPLE GIVEN
X CHROMOSOME.
SO WHAT I THINK AND AS AN
OPINION SEVERAL TIMES WE CAN'T
PROVE IT IS THAT THERE'S A HIGH
RECOMBINATION WEIGHT IN THE MALE
PAR 1.
BECAUSE OF THE Y CHROMOSOME GOES
ABOUT SEVEN OR EIGHT TIMES
HIGHER RECOMBINATION THAN XX
PAYERS.
AND I THINK THAT MAKES THEM MORE
PRONE TO MUTATIONS OR DELETIONS.
SO I THINK THAT THE HIGH RATE OF
BICUSPID VALVES AND AORTIC — IT
MUST BE A — X AND Y.
THE INSUFFICIENT STATE IN TURNER
SYNDROME UNCOVERS A HUGE
PROPENSITY TOWARD THIS
CONGENITAL PROBLEM.
SO I'M HOPING THAT PEOPLE, THE
SEX CHROMOSOMES HAVE BEEN A
BLACK BOX AT LEAST PARTICULARLY
THE Y IS SO DIFFICULT TO
SEQUENCE.
THE PSEUDO SOMAL REGIONS IS NOT
ON ANY GENOME-WIDE ARRAYS IT'S
NOT BEEN SUBJECTED TO — BECAUSE
IT'S A PROBLEM AREA.
I'M HOPING IN THE FUTURE THEY'LL
START LOOKING FOR Y CHROMOSOME
DELETIONS MUTATIONS IN THE MUCH
MORE COMMON MALES — 2% OF THE
MALES HAVE BICUSPID AORTIC
VALVES.
SO THAT WOULD BE RIPE FOR THE
PICKING.
>> ARE THERE ANY CLUES THOUGH AS
TO BEYOND THE GENETIC WHY THE
FUNCTIONAL STANDPOINT OVER WHAT
THE ETIOLOGY OF THIS PROPENSITY
FOR CORONARY HEART DISEASE AND
EXTRAORDINARY ASCENDING AORTA
DISSECTIONS.
>> NOT REALLY.
THEY HAVE SINGLE GENE MUTATIONS
IN MICE THAT CAUSE DIFFERENT
KIND OF DEFECTS BUT NOT THIS
INTERESTING CONSTELLATION OF
WHAT THEY CALL LEFT VENTRICULAR
OUTFLOWS DEFECTS.
THAT IS INVOLVING THE MICRO
VALVE, THE AORTIC VALVE, THE
THORACIC AORTA AND THE TURNER
SYNDROME HAS ALL OF THOSE VERY
COMMON DEFECTS IN COMBINATION OR
IN THE WHOLE COHORT.
AND THAT GROUP OF, THAT GROUP OF
DEFECTS IS FOUND IN FAMILIES SO
ONE FAMILY MEMBER WILL HAVE A
BICUSPID VALVE, THE OTHER WILL
HAVE A CORE, THE OTHER WILL
HAVE — SO THEY ARE LINKED
SOMEHOW.
I DON'T HAVE ANY CLUE HOW.
>> IS IT PATHOLOGY IDENTICAL
THAT OCCURS RANDOM.
>> PRETTY MUCH.
AORTIC DISSECTION IS ASSOCIATED
WITH AORTIC — MEDIA
DEGENERATION.
IT'S KIND OF A NON-SPECIFIC
FINDING.
>> DOES IT MATTER — THANK YOU
DR. BONDY FOR YOUR TALK BY THE
WAY.
I THINK YOU MIGHT HAVE ALLUDED
TO THIS OR SOMEBODY ALLUDED TO
THIS EARLIER.
DOES IT MATTER WHERE THE X CAME
FROM IN TERMS ON OF THE THE MOM
OR DAD.
>> IT DOESN'T MATTER IN THE
CONGENITAL HEART DEFECT.
IN OTHER WORDS THE FREQUENCY OF
BICUSPID VALVE IN 30% MIX M
PATIENTS AND MIX P PATIENTS
DIDN'T HAVE A CHANCE TO GO TO
WAS WE FIND MORE CORONARY HEART
DISEASE IN INPATIENTS.
MEN ARE PROFORCE XM MONO —
BECAUSE YOU GET TO Y FROM YOUR
DAD AND YOU HAVE TO GET YOUR X
FROM YOUR MOUTH.
SO MEN ARE ALL MONO SO MUCHIC
FOR XM AND THEY HAVE HIGH HEART
DISEASE RATE.
EARLY ONSET, MUCH MORE COMMON
THAN IN WOMEN.
AND THEY YOU KNOW, IN MALES
START SHOWING CALCIFICATION AND
THEIR CORONARY ARTERIES BY THE
AGE OF 30.
JUST YOU KNOW, IN
EPIDEMIOLOGICAL STATES.
SO WHY IS THAT?
WELL, IT'S NOT ESTROGEN.
THE ESTROGEN IS NOT PROTECTED.
THAT'S BEEN PRETTY MUCH WORKED
OUT AND WE THINK IT'S AN X
CHROMOSOME PARENTAL ORIGIN THAT
THE XM IS TRICKY.
IT'S JUST IS NOT A GOOD — IT'S
ASSOCIATED WITH HIGH RISK.
SO OUTPATIENTS WHO HAVE MATERNAL
X HAVE A MORE ANDROID PATTERN OF
ABNORMAL ADIPOSITY, AT A YOUNG
AGE VERY SIMILAR TO MEN.
WHEREAS THE XP PATIENTS HAVE NO
CALCIFICATION AND HAVE A MUCH
BETTER METABOLIC PROFILE.
WE THINK THE XP IS PROTECTED AND
THE XN IS RISKY FOR CORONARY
DISEASE.
WHY THAT WOULD BE I HAVE NO IDEA
YOU ABOUT IT COULD BE RELATED TO
SOME EARLY FUNCTION OF THESE X
CHROMOSOMES IN PLACENTAL
DEVELOPMENT, SOME TYPE OF
VASCULAR GENESIS.
ANY QUESTIONS FOR DR. BAKALOV ON
THE CLINICAL ASPECTS OR FOR
HOLLY WHAT IT'S LIKE TO HAVE
TURNER SYNDROMES.
>> HOW DO YOU DETECT CELIAC
DISEASE IN ANYONE WITH TURNER.
IS IT ANY DIFFERENT FROM WHAT IT
WOULD BE IN THE GENERAL
POPULATION.
>> NOT AT ALL.
[INDISCERNIBLE]
>> DO YOU ROUTINELY LOOK FOR
TRANSCONTAMASE DOES THAT THEN
BECOME THE DIAGNOSIS IN THE
ABSENCE OF SYMPTOMS OR ARE THESE
PEOPLE ASYMPTOMATIC.
>> [INDISCERNIBLE]
>> DO YOU THINK THESE AUTOIMMUNE
DISEASES IT'S A MATTER OF
SUSCEPTIBILITY THAT'S
FACILITATED BY SOMETHING THAT
TURNER SYNDROME RATHER THAN JUST
WHAT HAPPENS IN EVERYONE?
>> [INDISCERNIBLE]
>> SHOULD THEY SCREEN FOR TURNER
SYNDROME.
>> UNLESS THEY HAVE FAILURE AT
AGE 10.
>> ISN'T THERE AN INTERMEDIATE
DOSAGE EFFECT WHICH YOU'VE
ALLUDED TO SO THAT SOMEBODY WHO
HAS AN ABNORMALITY OF THIS
NATURE IN THE X CHROMOSOME,
THERE'S A GRADATION —
>> THERE ARE A VARIETY OF IMMUNE
SYSTEMS GENES ON THE X
CHROMOSOME AND A VARIETY OF MALE
DOMINANT IMMUNOLOGIC DISORDERS
ARE EXCELLENT.
SO IT SEEMS LIKE A ROLL
CONCLUSION THAT THERE'S SOME
ISSUE RELATED TO THE SPECIFIC
GENES, BUT WE DON'T KNOW WHAT IT
IS.
AND WE HAVE LOOKED.
>> IS THIS WHY WOMEN ARE SMARTER
THAN MEN.
>> THERE'S STUDY OF THESE
CHROMOSOME SITUATIONS TO
ELUCIDATE BUT NOTHING OBVIOUS
HAS TURNED UP AT ALL, YOU KNOW.
>> IT WAS NOTED THAT AUTISM
HDAD — IS INDEPENDENT OF
STEROID HORMONES THAT MANIFEST
ITSELF IN YOUNG BOYS WELL BEFORE
PUBERTY SO HE HYPOTHESIZED WITH
THE MATERNAL X CHROMOSOME THAT
WAS CONTRIBUTING SOME BAD
PSYCHIC EFFECT AND THAT X —
>> [INDISCERNIBLE]
>> RIGHT.
THAT'S RIGHT LACK OF SOCIAL
SKILLS MATCHES THE X CHMOSOME
ACCORDING TO THIS PSYCHIATRIST.
AUTISM AND SCHIZOPHRENIA, ONE
SPECTRUM OF MALE BAD BEHAVIOR.
POOR SOCIAL SKILLS.
SO ONE PERSON HAD THAT
HYPOTHESES THE XM GIRLS WOULD
HAVE POOR SOCIAL SKILLS AND BE
HAVE MORE COGNITIVE PROBLEMS
THAN XP GIRLS.
HE PUBLISHED A SHORT PAPER OF
THE NATURE SUGGESTING THAT
EVIDENCE — IT'S VERY HARD TO
CONFIRM PSYCHOLOGICAL COGNITIVE
STUDIES.
THEY ARE VERY SQUISHY.
AND SO I HAVEN'T THROWN OUT THAT
CONCEPT, BUT WE HAVEN'T BEEN
ABLE TO TRACK IT YET.
>> FOR THE HIGH RATE OF
DIAGNOSIS FOR TURNER SYNDROME IN
INFANTS, WHAT LEADS THE DOCTORS
TO SCREEN FOR OR LOOK FOR IF THE
HIGH DISPARITIES DON'T KNOW AS
MUCH UNTIL THEY'RE OLDER?
>> [INDISCERNIBLE]
IN THE NEWBORN IT'S VERY MUCH
EFFECTED.
>> [INDISCERNIBLE]
>> I WAS GOING TO ASK ABOUT
PRENATAL DIAGNOSIS.
DO YOU SEE A LOT OF PRENATAL
DIAGNOSIS NOW WITH ADVANCED
MATERNAL AGE AND WHAT DO YOU SEE
THAT AFFECTING THE NUMBERS AT
ALL?
>> YES.
>> THAT'S A LITTLE BIT OF A
LOADED QUESTION.
>> THAT'S ACTUALLY TRUE.
[INDISCERNIBLE]
DUE TO TERMINATION BECAUSE
SCREENING — IN JUST —
>> IS THE INCREASE INCIDENCE OR
REPORTING, IS THAT A REFLECTION
OF INCREASED AWARENESS OR IS
THERE SOMETHING IN OUR
ENVIRONMENT RAIDATION THAT IS
INFLUENCING CHROMOSOMAL
INACTIVATION.
>> [INDISCERNIBLE]
IS A MARKETING CAMPAIGN BY
PHARMACEUTICAL COMPANIES TO
[INDISCERNIBLE]
THIS WAS A HUGE EDUCATIONAL
CAMPAIGN [INDISCERNIBLE]
CHECK FOR KARYOTYPES.
I THINK THE GROWTH ORMONE
COMPANY IS LOOKING FOR A MARKET
ACTUALLY DID A GOOD SERVICE IN A
LOT OF EDUCATIONAL EFFORTS FROM
SAY 19 — WHENEVER RECOMBINANT
WAS FIRST DEVELOPED IN 1986 OR
SO.
WHAT DO YOU THINK, DR. BAKALOV.
>> YES [INDISCERNIBLE] ACTUALLY,
YOU KNOW, THE DIAGNOSIS OF SHORT
STATURE WE BECAME A DIAGNOSIS
BASICALLY.
>> BECAUSE OF THE TREATMENT.
YES, THERE IS A TREATMENT BUT AS
IT TURNS OUT, IT'S NOT A MAJOR
LIFE CHANGING THING FOR
[INDISCEIBLE] MAYBE HOLLY
CONFIRMED.
>> DO YOU THINK YOU'RE BETTER
OFF BEING FIVE FEET THAN YOU
WOULD HAVE BEEN IF YOU'RE FOUR
EIGHT.
>> I'M PERSONALLY HAPPY THAT I
TOOK GROWTH HORMONE BUT I DID
RESEARCH AND THERE WAS NO
CONFIRMATORY EVIDENCE THAT
THERE'S ANY CHANGE IN LIFE.
>> IN TERMS OF EDUCATION.
>> QUALITY OF LIFE.
>> MARRIAGE AND — THAT HEIGHT
DIDN'T SEEM TO MATTER, BUT
ALMOST EVERY PERSON I KNOW WITH
TURNER SYNDROME ARE HAPPIER
BEING AT FIVE FEET THAN FOUR
SIX.
FOUR SIX IS VERY SHORT.
PEOPLE PICK YOU UP, YOU'RE IN
PHYSICAL JEOPARDY BEING STEPPED
ON, PUSHED AROUND IT AND DRIVING
MAY BE IMPACT.
YOU MAY NEED A SPECIAL
APARTMENT.
>> I THINK IT MATTERS.
>> WE HAVEN'T BEEN AB TO MAKE
A CROSS EFFECTIVE ARGUMENT FOR
IT.
>> THERE DOESN'T SEEM TO BE ANY
DOWN SIDE.
>> ALL OF THIS HAPPENED BEFORE
THE BASEBALL PLAYERS DISCOVERED
GROWTH HORMONE, IS THAT RIGHT.
>> EXACTLY.
>> HI.
I JUST WONDERED IF ANOTHER
CHROMOSOME [INDISCNIBLE] THAT
ONE USUALLY GIVEN THE MENTAL
RETARDATION BUT THE PHYSICAL
FEATURE IS [INDISCERNIBLE] SO DO
YOU HAVE A STUDY COMPREHENSIVE
STUDY ABOUT THESE TWO SYNDROME
[INDISCERNIBLE] RELATIONSHIP
ABOUT MEANT ACTUAL AND PHYSICAL
FEATURES?
>> THERE ARE GENES THAT CAN BE
MUTE EIGHT IN MENTAL RETARDATION
BUT THE FACT THE FEMALE IS
MOSAIC.
REMEMBER SHE HAS RANDOM X
INACTIVATION
OFTEN TIMES IF ONE OF THE
CHROMOSOME'S DAMAGED OR HAS
EXPANDED FMR OR SOMETHING LIKE
THAT THAT IS PREFERENTIALLY
INACTIVATED.
E FEMALE HAS CHOICE BETWEEN
TWO X CHROMOSOME BECAUSE ONE OF
THEM IS SECOND MUTANT SHE CAN
EXPRESS THE OTHER ONE AND
OVERCOME AN EXCELLENT DEFECT.
SO THE FRAGILE X IS USUALLY ON
ONE SITE IN THE CHROMOSOME AND
INVOLVES AN EXPANSION OR
SHRINKAGE AND DOESN'T EFFECT THE
REST OF THE CHROME SO SO THE
DOESN'T INFLUENCE MUCH OF THE
PHENOTYPE THAT I'M AWARE.
I DON'T REALLY KNOW A WHOLE LOT
ABOUT IT.
>> [INDISCERNIBLE]
>> I'VE GOT A QUESTION.
YOU WERE TALKING ABOUT THE
DIFFICULTY IN THE — GOING TO
THE MITOSIS WHEN YOU'RE
FOLLOWG THE CHROMOSOMES.
THE QUESTION THAT I HAVE IS, IS
THERE AN INCREASED LEVEL OF
PREMATURE BIRTH IN TURNERS, ARE
THEY MORE OFTEN PREMATURE
BABIES?
>> [INDISCERNIBLE] IF YOU HAVE
THIS — A LOT OF ONE IN 200
CONCEPTS COULD BE TURNER
SYNDROME BUT ONLY ONE IN 2005
ARE BORN.
SO A LOT OF THOSE ARE
NON-VIABLE.
EARLY IN PREGNANCY.
USUALLY IT'S EARLY
PREGNANCY-WISE.
>> THE FIRST TRIMESTER AND IT
SEEMS TO BE IMPAIRED PLACENTA
FORMATION THEN IT'S MID LIKE SIX
MONTHS LATER IT'S DUE TO
CONGENITAL HEART DEFECTS.
LEFT HEART HYPERPLASIA OR AORTIC
INTERRUPTION.
THAT WAS INVOLVED IN THE
MIS
MISCARRIAGE OF A DEFORMED BABY
WITH HEART DISEASE.
>> IN OTHER WORDS FULL TERM AND
IMMATURELY BORN I'M NOT AWARE IF
IT'S INCREASE.
>> OKAY.
WELL I WANT TO THANK YOU ON
BEHALF OF ALL OF US, IT WAS
REALLY VERY EXCITING AND
INFORMATIVE.
[APPLAUSE]
>> THANK YOU VERY MUCH.
IT WAS A PLEASURE AND THANK YOU
RY MUCH.
BEST TO YOU.
GOOD OF GOOD FORTUNE THAT'S

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