Identification of exonic splicing enhancer sequences by analysis of dystrophin gene micromutation

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K21524
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Neurology
• Research Institution: Hyogo Medical University
• Principal Investigator: Shimomura Hideki 兵庫医科大学, 医学部, 講師 (30441273)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 筋ジストロフィー / スプライシング

Outline of Final Research Achievements

Progressive muscular dystrophy mainly develops due to genetic abnormality which result in decrease or lack muscle component. In cases of muscular dystrophy for which deletion / duplication mutations were not identified by the MLPA, we identified deletion or point mutations with a small number of nucleotides using direct nucleotide sequence or next-generation sequencer, and analyzed the splicing type in these cases. As a result, we were able to clarify the effect of small mutations on splicing. In analysis of the type 6 collagen gene, we found that two types of mRNA were produced by having two closely mutations on the same allele.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

本研究においては進行性筋ジストロフィーにおいてスプライシングに影響を及ぼす微小変異を明らかにした。今回の解析ではエクソン内配列の変異によりスプライシング異常を生じた症例は認められなかったため、ESEの同定は困難であったが、潜在的スプライシングサイトの活性化に関する知見が得られた。ESE制御とともに、潜在的スプライシングサイト制御による治療法の可能性が考えられた。