Q- A 4-year-old boy uses his hands to push himself up from the floor and has enlarged calves. His maternal uncle had the same disease. Which gene defect is most likely?
A- Frameshift deletion in the dystrophin gene
B- CGG repeat expansion in FMR1
C- Mutation in CFTR
D- Mutation in fibrillin-1
A- Frameshift deletion in the dystrophin gene. This is Duchenne muscular dystrophy, an X-linked recessive disease. The Gowers sign and calf pseudohypertrophy are classic, and CK is very high. Becker muscular dystrophy is milder because the deletion is in-frame. FMR1 causes fragile X syndrome, CFTR causes cystic fibrosis, and fibrillin-1 causes Marfan syndrome.
Q- A newborn has upslanting eyes, a single palmar crease, and an atrioventricular septal defect. The mother is 42 years old. What is the most common cause of this condition?
A- Meiotic nondisjunction
B- Robertsonian translocation
C- Mosaicism
D- Uniparental disomy
A- Meiotic nondisjunction. About 95% of Down syndrome (trisomy 21) cases are caused by maternal meiotic nondisjunction, and the risk increases with maternal age. About 4% are caused by Robertsonian translocation, which can be inherited, and about 1% are mosaic.
Q- A man developed chorea and dementia at age 45. His son develops the same disease at age 32. Which genetic phenomenon explains the earlier onset in the son?
A- Anticipation
B- Genomic imprinting
C- Incomplete penetrance
D- Mosaicism
A- Anticipation. In Huntington disease, the CAG repeat in the huntingtin gene (chromosome 4) tends to expand during spermatogenesis, so the disease starts earlier and is more severe in later generations. Anticipation is typical of trinucleotide repeat disorders such as Huntington disease, myotonic dystrophy, and fragile X syndrome.
Q- A child has poor muscle tone at birth and later develops an uncontrolled appetite with obesity, small hands and feet, hypogonadism, and intellectual disability. What is the most likely genetic cause?
A- Deletion of the paternal 15q11-q13 region
B- Deletion of the maternal 15q11-q13 region
C- Trisomy 18
D- 22q11.2 deletion
A- Deletion of the paternal 15q11-q13 region. This is Prader-Willi syndrome, an imprinting disorder. The maternal genes in this region are normally silenced, so loss of the paternal copy (by deletion or by maternal uniparental disomy) causes the disease. Loss of the maternal copy causes Angelman syndrome (happy demeanor, seizures, ataxia).
Q- Cystic fibrosis affects 1 in 2,500 newborns in a population. Assuming Hardy-Weinberg equilibrium, what is the approximate carrier frequency?
A- 1 in 25
B- 1 in 50
C- 1 in 100
D- 1 in 2,500
A- 1 in 25. The disease frequency q² = 1/2,500, so q = 1/50. Because p is close to 1, the carrier frequency 2pq ≈ 2 × 1/50 = 1/25.
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