A 14-month-old girl is evaluated in the pediatric genetics clinic for poor weight gain, recurrent respiratory infections, and greasy, foul-smelling stools. Physical examination reveals a weight below the 3rd percentile, a prominent forehead, a triangular face, and noticeable left-sided limb hypoplasia. Sweat chloride testing is elevated. Molecular genetic testing reveals the patient is homozygous for the mutation in the CFTR gene. Carrier screening of both parents, along with microsatellite analysis confirming paternity, shows the mother is a heterozygous carrier of the mutation, whereas the father has two normal CFTR alleles. What specific underlying molecular event is most likely responsible for this child's condition?
- Maternal isodisomy of chromosome 7Answer
- BMaternal heterodisomy of chromosome 7
- CGermline mosaicism in the paternal lineage
- DDe novo microdeletion of the paternal CFTR allele
- EPaternal deletion at chromosome 15q11-q13
Answer
Maternal isodisomy of chromosome 7
The correct answer accurately synthesizes the two distinct clinical presentations. The patient has Cystic Fibrosis (CF) and is homozygous for the CFTR mutation. Since only the mother is a carrier and paternity is confirmed, the child must have inherited two copies of the mother's mutant allele. This occurs via maternal isodisomy of chromosome 7. Crucially, maternal uniparental disomy of chromosome 7 is a known cause of Silver-Russell syndrome, an imprinting disorder characterized by severe growth retardation, a triangular face, prominent forehead, and body asymmetry. Maternal isodisomy of chromosome 7 is the only mechanism that comprehensively explains both the homozygous recessive condition (CF) and the imprinting disorder (Silver-Russell syndrome).
Step-by-Step Solution
Key Concept
Uniparental Isodisomy Unmasking Recessive Traits and Imprinting Disorders
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