Duchenne muscular dystrophy

The correct answer is D.

Duchenne muscular dystrophy (DMD) is a lethal, X-linked recessive disease affecting approximately 1 in 3300 live male births. The disease becomes symptomatic in early childhood. Inability to walk occurs by the end of the first decade, and death usually occurs by the second decade. Nearly all patients show the complete absence of the protein dystrophin, which is abundant in skeletal and cardiac muscle. The dystrophin gene (or DMD gene), located at Xp21, is approximately 2300 Kb in size, making it one of the largest known genes of any species. It contains 24 regions of 109 amino acids that are similar but not identical repeats of each other. In women, the similarity of these sequences can lead to the misalignment of homologous material at meiotic synapsis. In association with a recombination event, this misalignment gives rise to frameshift mutations, leading to an untranslatable mRNA. This series of events occurs at an extremely high rate of about 1 in 10,000. In fact, one third of DMD cases in each generation arise from this mechanism.

Diseases such as fragile X syndrome and Huntington disease are caused by the expansion of a trinucleotide repeat (choice A).

Infidelity (choice B) is not a plausible explanation for the child because the trait is an X-linked recessive condition. A male child must receive the DMD trait on the maternal X chromosome. The father of the child contributes only a Y chromosome, and the history stated that the mother had no family history of the disorder.

DMD in a patient with no family history is not generally due to a point mutation in the dystrophin gene (choice C).

Rare cases of DMD in females have been caused by an X chromosome-autosome translocation (choice E) with the breakpoint on the X chromosome within the DMD gene. Because of the translocation, only the cells in which the normal X chromosome is inactivated survive in the female zygote. This gives rise to a female who is heterozygous for the DMD gene but phenotypically expresses the disease.

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