Identification of causative genes of super-miscarriage and elucidation of human pregnancy maintain mechanism

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K09267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nagoya City University
• Principal Investigator: Sugiura Mayumi 名古屋市立大学, 医薬学総合研究院(医学), 教授 (30264740)
• Co-Investigator(Kenkyū-buntansha): 大石 久史 名古屋市立大学, 医薬学総合研究院(医学), 教授 (30375513)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 習慣流産 / 不育症 / 全ゲノム解析 / トリオ解析 / 妊娠メカニズム

Outline of Final Research Achievements

The causes of recurrent pregnancy loss (RPL) are antiphospholipid antibodies, chromosomal balanced translocations, uterine malformations, and fetal chromosomal aneuploidy, and about 25% of them have unknown true causes of euploid fetal chromosomes. The causative gene is identified by whole-genome trio analysis of Super miscarriage patients and their parents repeated more than 10 times and mouse genome editing.
A whole exon trio analysis of five families was performed and 13-27 candidate genes were narrowed down to each patient. New mutations were confirmed in TDRD15 and RUFY3 (family 4) and in PIPTNM1 and OR9K2 (family 2). Systemic rufy3 gene-deficient mice died shortly after birth, and heterofemale mice showed no clear differences in pregnancy and childbirth compared to wild-type.
A whole genome trio analysis of three families and one new family was performed and is currently being analyzed. Research continues with additional cases.

Free Research Field

Reproduction

Academic Significance and Societal Importance of the Research Achievements

Super流産の原因遺伝子は各家系に共通する必要はなく、原因遺伝子を見つけることで不育症の個別化治療を模索することができる。さらにこれらの遺伝子は着床に必須の遺伝子でもあり、ヒト妊娠メカニズムの解明にもつながる。