Lecture 7 Flashcards
what is the least common form of gene inheritance
X linked inheritance
how are X linked recessive inheritance caused
a mutation in a single gene on the X chromosome
explain why a male is hemizygous
a male with pathogenic variants is affected, he does not have a second X chromosome to compensate
how can the condition be recessive in the female carrier who is not affected
when her normal copy of the gene on her second X chromosome compensates
what is the commonest severe X-linked recessive disorder
Duchenne Muscular Dystrophy
what does Duchenne Muscular Dystrophy cause
- progressive muscle weakness and wasting from early childhood
- wheelchair bound in early teens
- death in late teens or early twenties
Symptoms of Duchenne Muscular Dystrophy
delayed walking - difficulty climbing stairs
late heart muscle involvement
- progressive muscle weakness
- scoliosis
what are the investigations for Duchenne Muscular Dystrophy
very high levels of creatine kinase in blood
Blood CK levels are a marker for muscle damage
how common is Duchenne Muscular dystrophy
1 in 5000 births
Haemophilia
lack of clotting factor in blood,
which normally allows formation of clots after injury
Hemophilia symptoms
bleeding after surgery
spontaneous bleeding into joints and muscles
Treatment of Hemophilia
replacement of deficient factors
X chromosome inactivation
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
how is X-inactivation controlled
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
causes of a female affected by an X-linked recessive disorder
- carrier mother marries an effected father
- Non-random X linked chromosome inactivation
- Turner’s syndrome
- X-autosome translocation
explain turners as a cause of female affected by an X linked recessive disorder
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
translocations
a type of chromosomal abnormality where a segment of one chromosome breaks off and attaches to another chromosome.
what are the two types of X linked dominant inheritance
- 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
rickets symptoms
short stature
bowed bones
what are most rickets due to
dietary or skin deficiency of vitamin D
family tree of an X linked disorder.
what is the chance of the child of an affected woman being affected
50:50
incontinentia pigmenti
X linked dominant disorder - lethal in males
mosaic patterns of skin pigmentation
