2019年7月
RNA sequencing solved the most common but unrecognized NEB pathogenic variant in Japanese nemaline myopathy.
Genetics in medicine : official journal of the American College of Medical Genetics
- 巻
- 21
- 号
- 7
- 開始ページ
- 1629
- 終了ページ
- 1638
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41436-018-0360-6
- 出版者・発行元
- NATURE PUBLISHING GROUP
PURPOSE: The diagnostic rate for Mendelian diseases by exome sequencing (ES) is typically 20-40%. The low rate is partly because ES misses deep-intronic or synonymous variants leading to aberrant splicing. In this study, we aimed to apply RNA sequencing (RNA-seq) to efficiently detect the aberrant splicings and their related variants. METHODS: Aberrant splicing in biopsied muscles from six nemaline myopathy (NM) cases unresolved by ES were analyzed with RNA-seq. Variants related to detected aberrant splicing events were analyzed with Sanger sequencing. Detected variants were screened in NM patients unresolved by ES. RESULTS: We identified a novel deep-intronic NEB pathogenic variant, c.1569+339A>G in one case, and another novel synonymous NEB pathogenic variant, c.24684G>C (p.Ser8228Ser) in three cases. The c.24684G>C variant was observed to be the most frequent among all NEB pathogenic variants in normal Japanese populations with a frequency of 1 in 178 (20 alleles in 3552 individuals), but was previously unrecognized. Expanded screening of the variant identified it in a further four previously unsolved nemaline myopathy cases. CONCLUSION: These results indicated that RNA-seq may be able to solve a large proportion of previously undiagnosed muscle diseases.
- リンク情報
-
- DOI
- https://doi.org/10.1038/s41436-018-0360-6
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/30467404
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000473518700022&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85057123885&origin=inward
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85057123885&origin=inward
- ID情報
-
- DOI : 10.1038/s41436-018-0360-6
- ISSN : 1098-3600
- eISSN : 1530-0366
- PubMed ID : 30467404
- SCOPUS ID : 85057123885
- Web of Science ID : WOS:000473518700022