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An approach to rapid characterization of DMD copy number variants for prenatal risk assessment
Author(s) -
Chin HuiLin,
O'Neill Kieran,
Louie Kristal,
Brown Lindsay,
SchladeBartusiak Kamilla,
Eydoux Patrice,
Rupps Rosemarie,
Farahani Ali,
Boerkoel Cornelius F.,
Jones Steven J. M.
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62349
Subject(s) - copy number variation , gene duplication , genetics , genetic counseling , genome , breakpoint , duchenne muscular dystrophy , computational biology , segmental duplication , biology , prenatal diagnosis , gene , chromosome , fetus , pregnancy , gene family
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 .