Two closely spaced mutations in cis result in Ullrich congenital muscular dystrophy

Hideki Shimomura; Tomoko Lee; Yasuhiko Tanaka; Hiroyuki Awano; Kyoko Itoh; Ichizo Nishino; Yasuhiro Takeshima

doi:10.1038/s41439-019-0052-z

Two closely spaced mutations in cis result in Ullrich congenital muscular dystrophy

Hum Genome Var. 2019 Apr 26:6:21. doi: 10.1038/s41439-019-0052-z. eCollection 2019.

Authors

Hideki Shimomura¹, Tomoko Lee¹, Yasuhiko Tanaka¹, Hiroyuki Awano², Kyoko Itoh³, Ichizo Nishino⁴, Yasuhiro Takeshima¹

Affiliations

¹ 1Department of Pediatrics, Hyogo College of Medicine, Nishinomiya, Japan.
² 2Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
³ 3Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁴ 4Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.

Abstract

A 2-year-old boy was diagnosed with Ullrich congenital muscular dystrophy (UCMD) by muscle biopsy. COL6A3 gene analysis by next-generation sequencing revealed two heterozygous splice-site mutations (c.6283-1 G > G/T and c.6310-2 A > A/T), whereas normal mRNA was produced. Genomic DNA analysis revealed two mutations located on the same allele; however, no mutation was detected in either parent. These results indicated that two closely spaced de novo mutations resulted in the autosomal dominant UCMD.

Keywords: Disease genetics; Neuromuscular disease.