Neuromuscular Disease-Related CNVs Detected in Clinical Exome Analysis

Investigators from the Netherlands searched for suspicious copy number variants (CNVs) in clinical exome sequences for thousands of individuals. As they report in the European Journal of Human Genetics, the researchers turned to the CoNIFER algorithm to search for CNVs in clinical exomes from 4,800 individuals with apparent muscle disorders, movement conditions, and/or neuropathy, unearthing candidate CNVs linked to disease-associated phenotypes for 88 individuals. When considered in concert with genetics-based diagnoses made previously, the authors note that CNVs were behind roughly 7 percent of genetic diagnoses achieved in the cohort so far. "CNVs varied from involvement of over 100 genes to single exons and explained X-linked, autosomal dominant, or -recessive disorders," they write, adding that the candidate CNVs uncovered often fell in genes that were consistent with individuals' symptoms or related conditions such as Parkinson's disease, Duchenne muscular dystrophy, or neuropathy. Based on these and other findings, the authors suggest that "CNV detection from [whole-exome sequencing] is worthwhile for movement disorders, muscle disease, neuropathies, or any other single system disorder, like vision disorders or renal disease."