Question
A 9-year-old boy presents with repeated joint bleeding episodes and is diagnosed with factor VIII deficiency. Considering the inheritance pattern of this disorder, which family member is most likely to also be affected?
A. His father
B. His maternal uncle
C. His paternal aunt
D. His mother
E. His paternal uncle
Answer
B. His maternal uncle
Detailed Explanation
This condition is Haemophilia A, caused by deficiency of factor VIII and inherited in an X-linked recessive manner.
Key principles of X-linked recessive inheritance:
- Males (XY) express the disease if they inherit one affected X chromosome.
- Females (XX) are usually carriers because they have one normal X chromosome compensating.
- There is no male-to-male transmission (father → son does NOT happen).
- The affected X chromosome must come from the mother in a male child.
In this case:
- The boy received his X chromosome from his mother.
- Therefore, the mutation must be present in the maternal line.
Why maternal uncle?
- The mother is likely a carrier.
- Her brother (maternal uncle) would have received the same X chromosome from their mother (maternal grandmother).
- Since he is male, if he inherited that X → he will be affected.
Why other options are incorrect:
- Father: Gives Y chromosome to son → cannot transmit X-linked disease to sons.
- Mother: Usually a carrier, rarely affected (needs two abnormal X chromosomes).
- Paternal aunt / paternal uncle: Belong to father’s lineage → not involved in transmission to son.
Cheat Sheet (Exam Gold 🔥)
X-linked recessive inheritance:
- Affects mostly males
- No father → son transmission
- Carrier mother →
- 50% sons affected
- 50% daughters carriers
- Affected male →
- All daughters = carriers
- All sons = normal
Classic examples:
- Haemophilia A (Factor VIII deficiency)
- Haemophilia B
- G6PD deficiency
- Duchenne muscular dystrophy
Most commonly affected relative in exams → Maternal uncle
Flashcards
Flashcard 1
Q: What is the inheritance pattern of haemophilia A?
A: X-linked recessive
Explanation: Gene located on X chromosome, manifests in males.
Flashcard 2
Q: Can a father pass haemophilia A to his son?
A: No
Explanation: Father gives Y chromosome to son.
Flashcard 3
Q: Which relative is commonly affected in X-linked recessive diseases?
A: Maternal uncle
Explanation: Shares maternal X chromosome.
Flashcard 4
Q: What is the probability a carrier mother has an affected son?
A: 50%
Explanation: Each son has a 1 in 2 chance of inheriting the defective X.
MCQs (High-Yield + Challenging)
MCQ 1
A boy is diagnosed with an X-linked recessive disorder. Which relative is most likely to also be affected?
A. Father
B. Maternal uncle
C. Paternal grandfather
D. Brother-in-law
Answer: B. Maternal uncle
Explanation: X-linked disorders are transmitted via the maternal line; maternal uncle shares same X source.
MCQ 2 (Which is FALSE?)
Regarding X-linked recessive inheritance:
A. Males are predominantly affected
B. Male-to-male transmission occurs
C. Carrier females are usually asymptomatic
D. Sons inherit X chromosome from mother
Answer: B. Male-to-male transmission occurs
Explanation: This is false; fathers pass Y chromosome to sons.
MCQ 3
A carrier female for haemophilia A has children. What is the chance her daughter is a carrier?
A. 25%
B. 50%
C. 75%
D. 100%
Answer: B. 50%
Explanation: Each daughter has 50% chance of inheriting affected X.
MCQ 4
Which of the following conditions follows X-linked recessive inheritance?
A. Marfan syndrome
B. Haemophilia A
C. Cystic fibrosis
D. Sickle cell disease
Answer: B. Haemophilia A
Explanation: Others are autosomal dominant or recessive.
MCQ 5
An affected male with haemophilia has children with a normal female. What is true?
A. All sons affected
B. All daughters affected
C. All daughters carriers
D. 50% sons affected
Answer: C. All daughters carriers
Explanation: Father passes affected X to all daughters.
MCQ 6 (Advanced)
A female expresses an X-linked recessive disorder. What is the most likely explanation?
A. She inherited mutation from father only
B. She is heterozygous carrier
C. She has Turner syndrome
D. She inherited Y chromosome
Answer: C. She has Turner syndrome
Explanation: Single X → no normal allele to compensate.
Summary for Quick Exam Revision
X-linked recessive disorders like haemophilia A predominantly affect males because they possess only one X chromosome, making them vulnerable to mutations inherited from their mother. Transmission occurs through carrier females, and crucially, there is no father-to-son transmission since fathers pass a Y chromosome to male offspring. The most commonly affected relatives are from the maternal side, especially the maternal uncle, as he shares the same X chromosome lineage. Carrier mothers have a 50% chance of having affected sons and 50% chance of having carrier daughters. Affected males pass the defective gene to all daughters (who become carriers) but none of their sons. Rare female expression occurs in conditions like Turner syndrome or homozygosity. Recognizing this inheritance pattern allows quick identification of likely affected family members, making “maternal uncle” a classic exam answer.