Bi‐allelic SPATA22 variants cause premature ovarian insufficiency and nonobstructive azoospermia due to meiotic arrest. Issue 5 (16th March 2022)

• Record Type: Journal Article
• Authors: Yao, Chencheng; Hou, Dong; Ji, Zhiyong; Pang, Dongmei; Li, Peng; Tian, Ruhui; Zhang, Yuxiang; Ou, Ningjing; Bai, Haowei; Zhi, Erlei; Huang, Yuhua; Qin, Yingying; Zhao, Jingpeng; Wang, Chenchen; Zhou, Zhi; Guo, Ting; Li, Zheng
• Is Part Of: Clinical genetics. Volume 101:Issue 5/6(2022)
• Page Start: 507
• Page End: 516
• Publication Date: 2022-03-16
• Subjects: gene variants -- meiosis -- NOA -- POI -- SPATA22; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.14129
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: The genetic causes of idiopathic premature ovarian insufficiency (POI) and nonobstructive azoospermia (NOA) remain unclear. We performed whole‐exome sequencing (WES) in members of a consanguineous family with two POI and two NOA patients to screen for potential pathogenic variants for familial POI and NOA. And a homozygous variant in SPATA22 (c.400C>T:p.R134X) was identified. Histological analysis and spermatocyte spreading assay demonstrated that the spermatogenesis was arrested at a zygotene‐like stage in the proband with NOA. The candidate gene was further screened in the in‐house WES database of idiopathic POI‐affected patients. One additional compound heterozygous variant in SPATA22 (c.900+1G>A and c.31C>T:p.R11X) was found in one patient with sporadic POI and validated by minigene assay. Thus, this is the first report identifying SPATA22 as the causative gene for human POI. Combined with the observations in the familial patient with NOA, our findings highlighted the essential role of meiotic HR genes in gametogenesis and gonadal function maintenance. Abstract : Bi‐allelic SPATA22 variants were identified in a Chinese consanguineous pedigree with two premature ovarian insufficiency (POI)‐affected patients and two NOA‐affected patients and one sporadic POI‐affected case. To the best of our knowledge, this is the first report identifying SPATA22 as the causative gene for human POI.