The identification of AMZ2 as a candidate causative gene in a severe teratozoospermia patient characterized by vacuolated spermatozoa  

作　　者：Liu Liu Jing Yang Wen-Jing Zhang Yi-Ling Zhou Gui-Jun Zhao Ya Huang Shu-Yan Tang 

机构地区：[1]Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200011,China [2]Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases,Shanghai 200011,China [3]State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development,Department of Computational Biology,School of Life Sciences,Fudan University,Shanghai 200436,China [4]Shanghai Towako Hospital,Shanghai 200131,China [5]Shanghai Institute of Medical Genetics,Shanghai Children's Hospital,Shanghai Jiao Tong University,Shanghai 200040,China

出　　处：《Asian Journal of Andrology》2024年第1期107-111,共5页亚洲男性学杂志（英文版）

基　　金：This study was supported by the National Natural Science Foundation of China(No.32200485);the University Synergy Innovation Program of Anhui Province(GXXT-2021-071);Shanghai Municipal Science and Technology Major Project(No.2017SHZDZX01).

摘　　要：Teratozoospermia with cephalic defects is one of the most severe types of sperm defects known to date.While several monogenic factors are linked to cephalic abnormalities,such as globozoospermia and macrozoospermia,the genetic cause of vacuolated spermatozoa remains inadequately described.Here,we analyzed whole-exome sequencing(WES)data for an individual from a consanguineous family with severely vacuolated spermatozoa.The analysis revealed a novel homozygous c.520A>G(p.Thr174Ala)variant in the archaelysin family metallopeptidase 2(AMZ2),a gene that encodes a zinc metalloprotease previously shown to be highly expressed in the testes and sperm.Multiple algorithms predicted this variant to be a damaging mutation.Consistent with an autosomal recessive mode of inheritance,this variant was inherited from heterozygous parental carriers.To investigate the potential pathogenicity of the identified variant,we compared the AMZ2 expression in sperm cells from the patient with the AMZ2 variant and from a healthy control.Immunoblot analysis revealed that the homozygous missense variant in AMZ2 abolished AMZ2 expression in the spermatozoa.Our findings reveal a candidate causative gene for vacuolated spermatozoa.

关 键 词：AMZ2 male infertility sperm quality TERATOZOOSPERMIA 

分 类 号：R698.2[医药卫生—泌尿科学]