Development of presumptive diagnostic methods for germ line mosaic variants using low frequency mosaic variants detection technologies

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Showa University
• Principal Investigator: Kato Mitsuhiro 昭和大学, 医学部, 教授 (10292434)
• Co-Investigator(Kenkyū-buntansha): 中村 和幸 山形大学, 医学部, 助教 (20436215)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: モザイク変異 / デジタルPCR / 遺伝相談

Outline of Final Research Achievements

The frequency of germline mosaic variants varies from disease to disease, and the frequency is often unknown, which is a hindrance to accurate genetic consultation. The purpose of this study is to develop diagnostic methods for low-frequency somatic mosaic variants and contribute to more accurate genetic counseling. We analyzed the causative genes for neurological diseases in children and identified 185 variants in 3 years. Mosaic was confirmed by digital PCR using a sample of a mother whose sample was initially considered to have no variant. A mosaic variant that was overlooked by the Sanger method was confirmed by digital PCR, and the mosaic rate was clarified. Accurate information is critical for genetic counseling in serious diseases, and analysis by Digital PCR would be recommended.

Free Research Field

小児神経学、臨床遺伝学

Academic Significance and Societal Importance of the Research Achievements

からだや細胞の一部に変異が起きて、正常と変異が混じった状態をモザイク変異と言います。血液では変異がなくても、精子や卵子などでモザイク変異を起こしていると次の子どもへの遺伝に影響します。私たちは、頻度が少ないモザイク変異の診断法を開発し、より正確な遺伝相談を行うための研究を行いました。小児神経疾患の原因遺伝子解析を行い、3年間で185例の変異をみつけました。両親には一見変異が認められませんでしたが、デジタルPCRという新しい解析手法により、ひとりの母親で5%の変異を確認することができました。重篤な病気の遺伝相談では、正確な情報提供がたいせつであり、デジタルPCRが役立つことを示しました。