Sex Chromosomes

Question 1

What different variants of Turner syndrome are seen.? And the proportions of each

Answer 1

50% 45,x
25% 46,x,abnormal x
12-20% 46,x,i(x)
15% mosaic
7% 45,x/46,xx/47,xxx
6-11% 45,x/46,xy and 45,x/46,x,+mar

Question 2

Phenotype of Turner syndrome

Answer 2

Short
Webbed neck
Gonadal dysfunction
Low hairline
Hypo plastic widely spaced nipples
Coarctation of aorta

Question 3

Phenotype of 47,xxx

Answer 3

Variable but most mild assymptomatic

Fertile

Question 4

What normal variants of y are seen?

Answer 4

Yqh+
Peri centric inv y
Satellites yq from acrocentric p arm
Y heterochromatin translocation a

Question 5

What Y chromosome deletions are there?

Answer 5

Azf a. Infertile. Oligo/azoospermia, serotoli syndrome
Azf b. Infertile Oligo/azoospermia
Alf c Most common. 90% Infertile Oligo/azoospermia but can often have Icsi

Question 6

What is the consequence of a balance x;autosome translocation in a male?

Answer 6

Infertility spermatogenic arrest caused by disruption of the sex vesicle

Question 7

What is the consequence of a balance x;autosome translocation in a female?

Answer 7

The normal x will have Xi (xist usually on der(x)

Approx half are infertile but more fertility could be tolerated due to Xi

Question 8

Considerations of an inherited balanced x;auto translocation in fetus

Answer 8

Fetal phenotype may not be same as mum due to Xi

Question 9

Where is the x inactivation centre located?

Answer 9

xq13

Question 10

Sex chromosome aneuploidies in men and clinical features

Answer 10

Klinefelter xxy- infertile,
Most common cause of male hypogonadism. Otherwise normal phenotype
Xxy - tall, fertile

Question 11

What non genetic causes of infertility should be considered?

Answer 11

Maternal age
Medication
Smoking 
Alcohol
Stress
Infection eg.mumps

Question 12

What is the definition of infertility?

Answer 12

Failure to achieve conception in one year

Question 13

What is the definition of infecundity?

Answer 13

Failure to sustain pregnancy to live born

Question 14

How are Y chromosome deletions investigated?

Answer 14

Pcr assay for polymorphic y Chr markers

Question 15

Female causes of infertility

Answer 15

Turner syndrome
X structural abnormality
T(X;auto) half are infertile
T(X;x)
Fragile X permutation carrier
Cf 20% thickening of cervical mucus

Question 16

What phenotype do you see with a ring X cintaining xist?

Answer 16

Variable ts - normal phenotype depending on deletion size and level

Question 17

What is the phenotype of an X ring with no xist present?

Answer 17

Usually small rings
No Xi then severe phenotype
Resemble kabuki syndrome

Question 18

How can Xi be measured?

Answer 18

Pcr assay of polymorphic cag repeat in exon 1 of androgen receptor gene at xq11.2

Question 19

What is the function of Xi?

Answer 19

Dosage compensation.

Question 20

Which region controls Xi?

Answer 20

XIC at xq13

Question 21

What does XIST rna do?

Answer 21

Cis acting rna. Coats chromatin in both directions. Required to initiate inactivation but not maintain it. Recruits histone variant macro H2A

Question 22

What is Tsix?

Answer 22

Transcribed fromXIST antisense. Represses XIST. A negative regulator of XIST. At inactivation the future inactive X stops expressing Tsix rna therefore increasing XIST expression

Question 23

How is X inactivation maintained?

Answer 23

High levels methylation law histone acetylation and MacroH2A accumulation

Question 24

Why are some regions of X not inactivated

Answer 24

For functional disomy

Question 25

How many X linked genes escape inactivation?

Answer 25

15%

Question 26

What is the classic X-y translocation and what phenotype does the unbalanced der(X) form confer into both sexes?

Answer 26

t(X;Y)(p22.3;q11). Der(X) unbalanced leads to infertility and mr in males but fertility and normal iq in females