A novel homozygous mutation in ACTL7A leads to male infertility.
Xiaopei ZhouQingsong XiWeimin JiaZhou LiZhenxing LiuGeng LuoChenxi XingDazhi ZhangMeiqi HouHuihui LiuXue YangYalin LuoXuejie PengGuihua WangTingting ZouLixia ZhuLei JinXianqin ZhangPublished in: Molecular genetics and genomics : MGG (2022)
Male infertility, a global public health problem, exhibits complex pathogenic causes and genetic factors deserve further discovery and study. We identified a novel homozygous missense mutation c.224A > C (p.D75A) in ACTL7A gene in two infertile brothers with teratozoospermia by whole-exome sequencing (WES). In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) showed fertilization failure of the two affected couples. The three-dimensional (3D) models showed that a small section of α-helix transformed into random coil in the mutant ACTL7A protein and mutant amino acid lacked a hydrogen bond with Ser170 amino acid. Immunofluorescence revealed that ACTL7A protein was degraded in sperms of patients. Transmission electron microscopy (TEM) analysis of sperms from the infertile patients showed that the irregular perinuclear theca (PT) and acrosomal ultrastructural defects. Furthermore, ACTL7A mutation caused abnormal localization and reduced the expression of PLCZ1 in sperms of the patients, which may be the key reasons for the fertilization failure after ICSI. Our findings expand the spectrum of ACTL7A mutations and provide novel theoretical basis for genetic counseling.
Keyphrases
- end stage renal disease
- public health
- amino acid
- chronic kidney disease
- newly diagnosed
- ejection fraction
- poor prognosis
- copy number
- small molecule
- binding protein
- insulin resistance
- pregnant women
- polycystic ovary syndrome
- men who have sex with men
- protein protein
- single cell
- high throughput
- intellectual disability
- pregnancy outcomes
- skeletal muscle