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

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,...

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Published inAsian journal of andrology Vol. 26; no. 1; pp. 107 - 111
Main Authors Liu, Liu, Yang, Jing, Zhang, Wen-Jing, Zhou, Yi-Ling, Zhao, Gui-Jun, Huang, Ya, Tang, Shu-Yan
Format Journal Article
LanguageEnglish
Published China Medknow Publications and Media Pvt. Ltd 01.01.2024
Medknow Publications & Media Pvt. Ltd
Wolters Kluwer - Medknow
Wolters Kluwer Medknow Publications
Subjects
Adult
amz2; male infertility; sperm quality; teratozoospermia
Analysis
Consanguinity
Exome Sequencing
Genes
Homozygote
Humans
Male
Metalloendopeptidases - genetics
Mutation, Missense
Original
Pedigree
Sperm
Spermatozoa
Spermatozoa - metabolism
Teratozoospermia - genetics
China
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Summary: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.
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These authors contributed equally to this work.
ISSN:1745-7262
1008-682X
1745-7262
1008-682X
DOI:10.4103/aja202321