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Volume 26, Issue 1 (January 2024) 26, 107–111; 10.4103/aja202321
The identification of AMZ2 as a candidate causative gene in a severe teratozoospermia patient characterized by vacuolated spermatozoa
Liu Liu 1 2, Jing Yang 3, Wen-Jing Zhang 4, Yi-Ling Zhou 1 2, Gui-Jun Zhao 5, Ya Huang 4, Shu-Yan Tang 1 2
1Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
2Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
3State 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.
4Shanghai Towako Hospital, Shanghai 200131, China.
5Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China.
Correspondence: Dr. SY Tang (sy_tang05@outlook.com) or Dr. Y Huang (sh_huangya@163.com)
Originally published: July 14, 2023 Received: December 11, 2022 Accepted: May 8, 2023
| Abstract |
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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.
Keywords: AMZ2; male infertility; sperm quality; teratozoospermia.
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