Diagnostic challenge using new methods in exome-negative patients

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07864
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kanagawa Children's Medical Center (Clinical Research Institute)
• Principal Investigator: Enomoto Yumi 地方独立行政法人神奈川県立病院機構神奈川県立こども医療センター(臨床研究所), 臨床研究所, 研究員 (20506290)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 全ゲノムシーケンス / 先天異常 / エクソン外変異 / 複雑構造変異 / エクソームシーケンス

Outline of Final Research Achievements

We performed whole genome sequencing (WGS) in exome-negative patients. WGS identified causal variants in two patients. One patient had a de novo variant in deep intronic region of the gene related his clinical features. Our functional study revealed that the variant resulted in aberrant splicing. The other patient (Rubinstein-Taybi syndrome) had scattered deletions including a partial 5’-untranslated region of CREBBP, but all coding exons in CREBBP were intact (two normal copies). Both variants were not identified by exome sequencing. This study using WGS identified the causative variants and elucidated the mechanism of disease in exome-negative patients.

Free Research Field

遺伝学

Academic Significance and Societal Importance of the Research Achievements

エクソーム解析では原因不明だった患者を対象に、全ゲノムシーケンスを用いた変異の探索を行った。結果、２名の患者の原因変異および疾患発症メカニズムを明らかにすることができた。本研究にてエクソーム解析の限界、全ゲノムシーケンス解析の可能性および課題が示された。今後の臨床シーケンス、遺伝学的研究の有用なデータになると思われる。