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Long-read whole-genome sequencing for the genetic diagnosis of dystrophinopathies.

ABSTRACT: 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.

SUBMITTER: Xie Z

PROVIDER: S-EPMC7545597 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Long-read whole-genome sequencing for the genetic diagnosis of dystrophinopathies.

Xie Zhiying Z Sun Chengyue C Zhang Siwen S Liu Yilin Y Yu Meng M Zheng Yiming Y Meng Lingchao L Acharya Anushree A Cornejo-Sanchez Diana M DM Wang Gao G Zhang Wei W Schrauwen Isabelle I Leal Suzanne M SM Wang Zhaoxia Z Yuan Yun Y

Annals of clinical and translational neurology 20200920 10

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 ...[more]

PMID: 32951359

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