• PMID: 30500349
• Gene Name: RNF220
• Condition: Male infertility
• Association: Associated
• Mutation: c. 56C>T [p. P19L]
• Population size: 1
• Population details: 1 infertile male
• Age: 32yrs
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

A homozygous RNF220 mutation leads to male infertility with small-headed sperm

Jiang X, Wang X, Zhang X, Xiao Z, Zhang C, Liu X, Xu J, Li D, Shen Y.

Morphological abnormality of spermatozoa head is a human infertility syndrome caused by spermatogenesis defects. The genetic alterations associated with macrozoospermia, globozoospermia and acephalic spermatozoa are relatively definite, whereas the underlying pathogenesis of small-headed sperm remains unclear. Here, we report a 32-year-old infertile male from a consanguineous family, who presented with 95% of small-headed sperm. Subsequent whole-exome sequencing (WES) analysis identified a homozygous mutation (c. 56C>T [p. P19L]) in Ring Finger Protein 220 (RNF220) gene, which is dominantly expressed in testis. RNF220 protein is an E3 ligase promoting the ubiquitination and proteasomal degradation of SIN3 Transcription Regulator Family Member B (SIN3B), a chromatin-associated protein, which is primarily expressed in the nucleus of germ cells and plays a vital role in chromatin condensation. Notably, this variant could promote the RNF220 protein degradation leading to excessive condensed chromatin in the sperm through the medium SIN3B. Therefore, our study is the first to identify an autosomal recessive genetic mutation in RNF220 that was responsible for small-headed sperm in humans by regulating the expression of chromatin-associated protein SIN3B. CI - Copyright © 2018 Elsevier B.V. All rights reserved. FAU - Jiang, Xiaohui AU - Jiang X AD - Human Sperm Bank, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China. FAU - Wang, Xiang AU - Wang X AD - Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China. FAU - Zhang, Xueguang AU - Zhang X AD - Department of Obstetrics/Gynecology, Joint Laboratory of Reproductive Medicine (SCU-CUHK), Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China. FAU - Xiao, Zhun AU - Xiao Z AD - Reproduction Medical Center of West China Second University Hospital, Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu 610041, China. FAU - Zhang, Chaoliang AU - Zhang C AD - State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. FAU - Liu, Xiaojun AU - Liu X AD - Peking Medriv Academy of Genetics and Reproduction, Peking 102629, China. FAU - Xu, Jinyan AU - Xu J AD - Human Sperm Bank, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China. FAU - Li, Dingming AU - Li D AD - Human Sperm Bank, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China.