Genetics Single Gene Defect (XLR,XLD,Y-linked) Flashcards
Duchenne Muscular Dystrophy is an XLR disorder where the gene, dystrophin is affected.
How does the pathogenic variant causes the symptoms of DMD?
[…]
Does the absence of signs or symptomes exclude carrier status in girls?
[…]
What are the possible scenarios and hence risk of recurrence?
[…]
Duchenne Muscular Dystrophy is an XLR disorder where the gene, dystrophin is affected.
How does the pathogenic variant causes the symptoms of DMD?
**pathogenic variant causes gene to not produce any dystrophin protein (loss of function). Hence boys with DMD have muscle degeneration, manifesting as **
- High creatine kinase level in the blood
- Progressive muscle weakness
- Death in the second decade of life if not treated
Does the absence of signs or symptomes exclude carrier status in girls?
NO!
What are the possible scenarios and hence risk of recurrence?
- If mother is a carrier, RoR = 25%
- if mother germline mosaicism, RoR = observational data = 1-10%
- If new spontaneous mutation, RoR = low
If a daughter’s XLD condition was due to a hemizygous father, the risk in the mother’s next pregnancy is
Son: […]%
Daughter: […]%
If a daughter’s XLD condition was due to a hemizygous father, the risk in the mother’s next pregnancy is
Son: 0%
Daughter: 100%
Cuz son means cfm will get Y from father, whereas daughter means cfm will get pathogenic variant X from father.
If a woman has a son with an XLR disorder, the son’s condition may due to one of the following senarios (IMPT)
[…]
If a woman has a son with an XLR disorder, the son’s condition may due to one of the following senarios (IMPT)
- Inheritance from a carrier mother (risk of recurrence = 25%)
- Inheritane from a mother with germline mosaicism (risk of recurrence = observational data)
- Spontaneous mutation (risk of recurrence = low)
In X-linked diseases, males have a more severe phenotype because they only have one X chromosome. Why females have variable/less severe phenotypes?
[…]
In X-linked diseases, males have a more severe phenotype because they only have one X chromosome. Why females have variable/less severe phenotypes?
X-inactivation, homozygosity (rare)
“Homozygous describes the genetic condition or the genetic state where an individual has inherited the same DNA sequence for a particular gene from both their **biological mother **and their biological father.”
Its rare for both father and mother to have the pathogenic variant on X chromosome
Phenotypic heterogeneity vs Genetic heterogeneity?
[…]
Phenotypic heterogeneity vs Genetic heterogeneity?
Phenotypic heterogeneity means one genotype giving rise to 2 or more phenotype
Genetic heterogeneity means 1 phenotype caused by 2 or more genotypes
Since females are fine without having Y chromosome, the Y chromosome must code for genes that are either […] or are […]
Since females are fine without having Y chromosome, the Y chromosome must code for genes that are either specific to male function or are non-essential
e.g deletion of q arm of Y chromosome gives rise to infertility
What are examples of XLD disorders?
[…]
What are examples of XLD disorders?
- Incontinentia Pigmenti
- X-linked Hypophosphatemic Rickets
What are some characteristics of X-linked recessive disorders?
[…]
What are some characteristics of X-linked recessive disorders?
-* Incidence of disorder is higher in males than in females*
- Affected male may have inherited that affected gene from his mother (carrier) or may represent a new spontaneous mutation
- Affected male will never transmit affected gene to his sons, but all daughters will receive the affected gene
Note that all males receive their X from mother!!! Father have to give Y for the child to be male
What are some examples of XLR diseases?
[…]
What are some examples of XLR diseases?
- Red-green colour blindness
- G6PD deficiency
- Duchenne Muscular Dystrophy
- Haemophilia A
“Righteous Girls Destroys Hamsters”
What are the characteristics of XLD disorders?
[…]
What are the characteristics of XLD disorders?
-* gives rise to disorder in hemizygous males and heterozygous females*
-* Seen more frequently in females than in males*
- Males usually more affected
-* affected child usually have affected parent (small proportion due to germline mosaicism/new mutations*
- IMPT: Affected male transmit affected gene to ALL daughters but NO sons
What are the characteristics of Y-linked disorders?
[…]
What are the characteristics of Y-linked disorders?
- affects only males
- males always have an affected father unless it is due to a new mutation
- all sons of affected male will be affected
- all daughters of affected male will NOT be afffected
