Comprehensive analysis of causative gene in familial congenital heart disease by whole exome analysis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17357
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Nagoya University
• Principal Investigator: YAMAMOTO Hidenori 名古屋大学, 医学部附属病院, 医員 (80801662)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 先天性心疾患 / 全エクソーム解析 / プロテオーム解析 / チロシンキナーゼ / 22q11.2欠失症候群

Outline of Final Research Achievements

The causative genes were searched for in 3 families with hereditary congenital heart disease, which were revealed in all families.
One of them was a novel mutation in ABL1. The onset mechanism of congenital heart disease due to abnormal ABL1 has not been elucidated at all, and experiments using cultured cells revealed increased phosphorylation of UFD1. We reported this as the first study to examine the onset mechanism of congenital heart disease associated with ABL1 abnormalities.
In the other two families, new gene abnormalities of TBX20 (submitting) and gene Y (preparing for functional analysis experiment) were found, respectively.

Free Research Field

遺伝性心疾患

Academic Significance and Societal Importance of the Research Achievements

先天性心疾患の約10%が単一遺伝子異常に由来すると考えられているが、本研究で対象としたような多数の発症者を含む大家系では、網羅的遺伝子解析を行うことで、非常に高率に原因遺伝子が判明することが示された。
単一遺伝子異常に由来する先天性心疾患は、原因遺伝子によって発症しうる心疾患がある程度予測可能であるため、原因遺伝子を判明させることは、次子・次世代の発症リスクの予測や、将来的には出生前診断、着床前診断に有用となる可能性が示唆される。