Open AccessLong‐read whole‐genome sequencing for the genetic diagnosis of dystrophinopathies
Author(s) -
Xie Zhiying,
Sun Chengyue,
Zhang Siwen,
Liu Yilin,
Yu Meng,
Zheng Yiming,
Meng Lingchao,
Acharya Anushree,
CornejoSanchez Diana M,
Wang Gao,
Zhang Wei,
Schrauwen Isabelle,
Leal Suzanne M.,
Wang Zhaoxia,
Yuan Yun
Publication year - 2020
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51201
Subject(s) - dystrophin , whole genome sequencing , medicine , genetic diagnosis , genome , computational biology , genetic testing , genetics , dna sequencing , muscular dystrophy , gene , biology
The precise genetic diagnosis of dystrophinopathies can be challenging, largely due to rare deep intronic variants and more complex structural variants (SVs). We report on the genetic characterization of a dystrophinopathy patient. He remained without a genetic diagnosis after routine genetic testing, dystrophin protein and mRNA analysis, and short‐ and long‐read whole DMD gene sequencing. We finally identified a novel complex SV in DMD via long‐read whole‐genome sequencing. The variant consists of a large‐scale (~1Mb) inversion/deletion‐insertion rearrangement mediated by LINE‐1s. Our study shows that long‐read whole‐genome sequencing can serve as a clinical diagnostic tool for genetically unsolved dystrophinopathies.