Lecture 7

Question 1

what is the least common form of gene inheritance

Answer 1

X linked inheritance

Question 2

how are X linked recessive inheritance caused

Answer 2

a mutation in a single gene on the X chromosome

Question 3

explain why a male is hemizygous

Answer 3

a male with pathogenic variants is affected, he does not have a second X chromosome to compensate

Question 4

how can the condition be recessive in the female carrier who is not affected

Answer 4

when her normal copy of the gene on her second X chromosome compensates

Question 5

what is the commonest severe X-linked recessive disorder

Answer 5

Duchenne Muscular Dystrophy

Question 6

what does Duchenne Muscular Dystrophy cause

Answer 6

• progressive muscle weakness and wasting from early childhood
• wheelchair bound in early teens
• death in late teens or early twenties

Question 7

Symptoms of Duchenne Muscular Dystrophy

Answer 7

delayed walking - difficulty climbing stairs

late heart muscle involvement

• progressive muscle weakness
• scoliosis

Question 8

what are the investigations for Duchenne Muscular Dystrophy

Answer 8

very high levels of creatine kinase in blood
Blood CK levels are a marker for muscle damage

Question 9

how common is Duchenne Muscular dystrophy

Answer 9

1 in 5000 births

Question 10

Haemophilia

Answer 10

lack of clotting factor in blood,
which normally allows formation of clots after injury

Question 11

Hemophilia symptoms

Answer 11

bleeding after surgery
spontaneous bleeding into joints and muscles

Question 12

Treatment of Hemophilia

Answer 12

replacement of deficient factors

Question 13

X chromosome inactivation

Answer 13

early in embryogenesis in females, one of the two X chromosomes in each cell is randomly inactivated by the addition of methyl groups to the chromosomal DNA

Question 14

how is X-inactivation controlled

Answer 14

control is directed by XIST itself a gene on the X chromosome

XIST controls methylation of most of the genes on the X chromosome to inactivate them

Question 15

causes of a female affected by an X-linked recessive disorder

Answer 15

1. carrier mother marries an effected father
2. Non-random X linked chromosome inactivation
3. Turner’s syndrome
4. X-autosome translocation

Question 16

explain turners as a cause of female affected by an X linked recessive disorder

Answer 16

in classical turners, a woman only has a single X chromosome

if this X chromosome has a pathogenic variant in a gene on the X chromosome, she will also show that X linked disorder

Question 17

translocations

Answer 17

a type of chromosomal abnormality where a segment of one chromosome breaks off and attaches to another chromosome.

Question 18

what are the two types of X linked dominant inheritance

Answer 18

• x linked dominant disorder that affects both males and females, but females may be less affected
• X linked dominant which affects females only, pathogenic variant is lethal in hemizygous male pregnancies

Question 19

rickets symptoms

Answer 19

short stature
bowed bones

Question 20

what are most rickets due to

Answer 20

dietary or skin deficiency of vitamin D

Question 21

family tree of an X linked disorder.
what is the chance of the child of an affected woman being affected

Answer 21

50:50

Question 22

incontinentia pigmenti

Answer 22

X linked dominant disorder - lethal in males

mosaic patterns of skin pigmentation