Sex Chromosomes

Question 1

Size of X and Y chromosomes

Answer 1

X = 153 Mb, 195 known gene loci 
Y= 50 Mb and 13 known loci (4 in common with X)

Question 2

What region do X and Y share?

Answer 2

Xpter/Ypter pseudoautosomal region (PAR1) 2.6 mb

Par2 at X/Yqter

Question 3

What gene is present in PAR1

Answer 3

Shox gene

Question 4

What happens regions of asynopsis on x and y at meiosis

Answer 4

Not tolerated at meiosis so form sex vesicles

Question 5

Where is the x inactivation centre (XIST)?

Answer 5

Xq13

Question 6

Disruption of what area of X is associated with gonadal dysgenesis?

Answer 6

Xp11.2-p22.1

Question 7

Where is the X critical region?

Answer 7

Xq13-q26

Breakpoints in this region associated with gonadal dysgensis

Question 8

Breakpoints in what area of the X critical region is not associated with gonadal dysgenesis?

Answer 8

Xq22

Question 9

Where is the SRY gene? What does sry do?

Answer 9

Proximal to PAR on the short arm.

It is the testis determining factor (TDF)

Question 10

Where is the gonadoblastoma specific region (GBY)?

Answer 10

Proximal Yq (just blow centromere)

Several genes associated with infertility

Question 11

Features of distal Yq?

Answer 11

Heterochromatic block 
Non-coding
Variable length 
Q banding and c band positive 
DAPI Bright on FISH

Question 12

Incidence of turner?

Answer 12

1:2000- 1:5000

Question 13

True or false: turner is associated with older mother?

Answer 13

False- associated with older father- often male X missing

Question 14

Signs of turner in utero?

Answer 14

Cystic hygroma (excess fluid at nape of neck) 
Inter uterine growth retardation

Question 15

Symptoms of turners in newborns

Answer 15

Small for dates

Lymphadema (excess fluid beneath the skin) of hands and feet

Question 16

Symptoms of turner in childhood?

Answer 16

Short stature (98%)
High arched palate (82%)
Short neck/low hairline (80%)
Hypoplastic widely spaced nipples (78%)

Question 17

Features of turners in adolescence ?

Answer 17

Short stature
Primary ammenorrhea
Delayed puberty

Question 18

Most common cytogenetics for turner?

Answer 18

55% 45,X
25% 46,X, abnormal X
12-20% 46,X, i(X)(q10)
15% mosaic
Numerical 
Structural

Question 19

Classic Turner syndrome symptoms

Answer 19

20-30% congenital heart malformations
30-60% structural anomalies of kidneys
Streak ovaries
Infertile

Question 20

45,X/46,XX phenotype

Answer 20

Taller
Likely secondRy amenhorrea rather than primary
May be fertile /subfertile

Question 21

Phenotype of 45 x/ 46 x, i(x)(q10) or ring r(x)?

Answer 21

Less turner. Only short stature and gonadal dysgenesis

Mitotically unstable structural abnormality results in post zygotic generation of the 45,x cell line

Question 22

What is phenotype of 45x /46x with marker of y origin.?

Answer 22

Female may be at increased risk of gonadoblastoma (benighted tumour that can turn malignancy)

Question 23

Where is the gonadoblastoma gene found?

Answer 23

Proximal Yq. Critical region GBY has candidate gene TSPY

Question 24

True or false: turner phenotype is less severe if Xist is absent

Answer 24

False: more sever if absent

Functional disomy!!!!

Question 25

Treatment for turner?

Answer 25

Growth hormone treatment for height Puberty- treat with oestrogen and progesterone Fertility- oocyte donation- embryo transplant If Y present - surgery to remove streak ovaries

Question 26

Frequency of Klinefelter syndrome

Answer 26

1/500-1/1000

Question 27

When do klinefelters usually present?

Answer 27

As adults with fertility issues | Occasionally as children with LD

Question 28

Clinical features of klinefelters?

Answer 28

30%-50% gynaecomastia (increased breast carcinoma) Infertility/azoospermia Eunuchoid habitus (f minute body type) IQ reduced relative to sibs

Question 29

Common other chromosomal cases of male infertility

Answer 29

45 x/ 46 xy Y structural abnormalities Isodicentric y, r(y) Robertsonian translocation (or other translocation especially involving Acrocentric)

Question 30

Features of 47, XYY

Answer 30

1 in 840 Mild clinical manifestation Tall, prominent forehead, maybe associated with behaviour problems Normal fertility

Question 31

Features of 47, XXX

Answer 31

1 in 1000 newborns Essentially normal phenotype Mild Devdel and motor delay wide variation May have increased risk of having xxx or xxy offspring

Question 32

48, xxxx

Answer 32

``` Iq 30-80 Normal to tall stature Speech delay Downs like features- epicanthic folds, midface hypoplasia Menstrual disorders, reduced fertility Additional Xs are maternally derived ```

Question 33

49,XXxX

Answer 33

Moderate to severe MR Prenatal onset growth deficiency Microcephaly Downs like features

Question 34

48,xxxy

Answer 34

``` Moderate to mild Genital hypoplasia (reduced in size) Mild dismorphisms Normal height Usually additional xs from mother ```

Question 35

49, XXXXY

Answer 35

``` Moderate to severe (iq 30) Low birth weight Short stature Hypogonadism Downs like features ```

Question 36

What does the Shox gene do?

Answer 36

Short stature homeobox gene | Deletions found in idiopathic short stature

Question 37

What disorder is caused by mutations in the shox gene?

Answer 37

Leri-Weill dyschrondrosteosis (lwd) | Characteristic by disproportionate short stature and a curving of radius (modelling deformity)

Question 38

What is the mode of inheritance of mutations in the shox gene?

Answer 38

LWD - pseudoautosomal dominant disorder | Depends on genetic recombination between x and y

Question 39

What disorder is caused by a homozygous loss of the SHOX gene?

Answer 39

Langer mesolmelic dysplasia (shortening of arms and legs =mesomelia)

Question 40

Symptoms of Kallmann syndrome?

Answer 40

Anosmia (no smell) due to agenesis of the olfactory lobes Hypogonadism secondary to deficiency of hypothalamic gonadotropin-releasing hormone (GnRH) Mild MR Colour blindness

Question 41

2 forms of kallmann syndrome

Answer 41

1) AD due to LOF mutations in fibroblast growth factor receptor-1 (FGFR1) 2) sex linked form due to mutation in KAL1 close to PAR

Question 42

Why is there a higher prevalence of Kallmann syndrome in males?

Answer 42

KAL1 partially escapes X inactivation

Question 43

Where is KAL1 located?

Answer 43

Do

Question 44

What is the cause of X-linked Icthyosis (lizard like)

Answer 44

Generalised scaling of the skin | Placental steroid sulfatase (STS) deficiency

Question 45

What is the cause of x-linked icthyosis?

Answer 45

Complete o partial deletion of the STS gene mapped to Xp22.3