An approach to rapid characterization of DMD copy number variants for prenatal risk assessment

Am J Med Genet A. 2021 Aug;185(8):2541-2545. doi: 10.1002/ajmg.a.62349. Epub 2021 May 21.


Prenatal detection of structural variants of uncertain significance, including copy number variants (CNV), challenges genetic counseling, and creates ambiguity for expectant parents. In Duchenne muscular dystrophy, variant classification and phenotypic severity of CNVs are currently assessed by familial segregation, prediction of the effect on the reading frame, and precedent data. Delineation of pathogenicity by familial segregation is limited by time and suitable family members, whereas analytical tools can rapidly delineate potential consequences of variants. We identified a duplication of uncertain significance encompassing a portion of the dystrophin gene (DMD) in an unaffected mother and her male fetus. Using long-read whole genome sequencing and alignment of short reads, we rapidly defined the precise breakpoints of this variant in DMD and could provide timely counseling. The benign nature of the variant was substantiated, more slowly, by familial segregation to a healthy maternal uncle. We find long-read whole genome sequencing of clinical utility in a prenatal setting for accurate and rapid characterization of structural variants, specifically a duplication involving DMD.

Keywords: DMD; Duchenne muscular dystrophy; copy number variant; long-read sequencing; prenatal genetic testing; structural variant.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Chromosome Breakpoints
  • Chromosome Duplication
  • Chromosomes, Human, X
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations*
  • Dystrophin / genetics*
  • Exons
  • Female
  • Genetic Association Studies / methods
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Humans
  • Male
  • Muscular Dystrophy, Duchenne / diagnosis*
  • Muscular Dystrophy, Duchenne / genetics*
  • Pedigree
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Sequence Analysis, DNA


  • DMD protein, human
  • Dystrophin