De novo copy-number variant — MRCPsych Paper A MCQ

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ModerateGeneticsDe novo copy-number variantMRCPsych Paper A

A 7-year-old boy with global developmental delay and autism undergoes trio chromosomal microarray testing. A pathogenic deletion at 16p11.2 is identified in the child but is not detected in either biological parent; parentage is confirmed. Which term best describes the origin of this genomic finding?

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Correct answer: D — De novo copy-number variant

The correct answer is D. A copy-number change identified in the child but absent from both confirmed biological parents is classified as a de novo copy-number variant: it arose in a parental germ cell or after fertilisation rather than being inherited as the same variant from a parent. Pathogenic de novo CNVs are recognised contributors to autism and developmental delay. X-linked recessive transmission does not explain an autosomal chromosome 16 deletion. Mitochondrial inheritance is maternal and concerns mitochondrial DNA, not this autosomal CNV. Autosomal recessive inheritance generally requires pathogenic variants affecting both alleles and does not describe this parent–child segregation pattern. Chromosome 15 imprinting disorders involve parent-of-origin effects at specific chromosome 15 loci, not a 16p11.2 deletion.

Reference: Sebat J et al. Strong association of de novo copy number mutations with autism. Science. 2007;316:445–449. https://pubmed.ncbi.nlm.nih.gov/17363630/