Compound Heterozygous Variants in ZSWIM7 Gene Linked to Infertility and Its Role in Gonadal Development.

Area of Science:

• Genetics
• Reproductive Biology
• Molecular Biology

Background:

• Infertility affects a significant portion of the population, with genetic factors playing a crucial role.
• Premature ovarian insufficiency (POI) and azoospermia are major causes of reproductive failure.
• The ZSWIM7 gene's role in human reproduction remains incompletely understood.

Purpose of the Study:

• To investigate the association between ZSWIM7 gene variants and the etiology of infertility.
• To characterize the genetic basis of infertility in a patient with primary amenorrhea and hypogonadism.
• To explore the functional impact of ZSWIM7 loss-of-function variants on gonadal development.

Main Methods:

• Whole-genome sequencing (WGS) to identify gene variants and copy number variations (CNVs).
• G-banding karyotype analysis and FMR1 premutation testing.
• In silico network analysis to predict gene interactions.

Main Results:

• Identified compound heterozygosity for ZSWIM7 variants in a patient with primary amenorrhea: a pathogenic single-nucleotide variant (SNV) and a gene deletion.
• This represents the first reported case of compound heterozygosity for ZSWIM7 involving both a base deletion and a CNV.
• In silico analysis revealed ZSWIM7 interacts with genes critical for DNA repair and gonadal development.

Conclusions:

• Loss-of-function pathogenic variants in ZSWIM7 are associated with infertility in both sexes.
• ZSWIM7 plays a critical role in the formation and maintenance of male and female gonads.
• These findings expand the understanding of genetic causes of infertility and highlight ZSWIM7 as a potential therapeutic target.