Long-Read Sequencing Revealed Extragenic and Intragenic Duplications of Exons 56–61 in DMD in an Asymptomatic Male and a DMD Patient

Frontiers in Genetics

Ju Liu¹  Yue Sun²  Lina Liu²  Ying Bai²  Jingjing Li²  Li Wang²  Xiangdong Kong²  Jinghan Xu²  Cangcang Jia³  Yong Gao³ 

[1] Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;GrandOmics Biosciences, Beijing, China;

关键词: Duchenne muscular dystrophy;    breakpoint analysis;    DMD duplication;    long-read sequencing;    whole-exome sequencing;   

DOI  :  10.3389/fgene.2022.878806

来源: DOAJ

【 摘 要 】

Expanded carrier screening (ECS) has become an increasingly common technique to assess the genetic risks of individuals in the prenatal or preconception period. Unexpected variants unrelated to referral are being increasingly detected in asymptomatic individuals through ECS. In this study, we reported an asymptomatic male with duplication of exons 56–61 in the DMD gene through ECS using whole-exome sequencing (WES), which was also detected in a male patient diagnosed with typical Duchenne muscular dystrophy (DMD). Breakpoint analysis was then performed to explore the potential mechanisms of phenotypic differences using long-read sequencing (LRS), PacBio single-molecule real-time (PacBio SMRT) target sequencing, and Sanger sequencing. Complex structural variations (SVs) on chromosome X were identified in the asymptomatic male, which revealed that the duplication occurred outside the DMD gene; whereas, the duplication in the patient with DMD was a tandem repeat. The phenotypic differences between the two men could be explained by the different breakpoint junctions. To the best of our knowledge, this is the first report of a breakpoint analysis of DMD duplication in two men with different phenotypes. Breakpoint analysis is necessary when the clinical phenotypes are inconsistent with genotypes, and it applies to prenatal testing.

【 授权许可】

Unknown