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We investigated an 18\u2010year\u2010old female patient who presented with primary amenorrhea, hypoplasia of the uterus and ovaries, Tanner stage II breast and pubic hair development, severe scoliosis (surgically repaired), recurrent urinary infections, and hypothyroidism. Genetic analysis revealed two heterozygous variants: a loss\u2010of\u2010function frameshift mutation in <jats:italic>ZSWIM7<\/jats:italic> and a chromosomal deletion encompassing the same gene\u2014a combination not previously described in the literature. Diagnostic techniques included G\u2010banding karyotype analysis, evaluation of <jats:italic>FMR1<\/jats:italic> premutation by PCR, and whole\u2010genome sequencing to identify gene variants and copy number variations (CNVs). The patient carries a pathogenic single\u2010nucleotide variant (SNV) and, in the other chromosome, a deletion encompassing the <jats:italic>ZSWIM7<\/jats:italic> gene. In silico network analysis indicated that <jats:italic>ZSWIM7<\/jats:italic> interacts with genes involved in DNA repair and gonadal development. A literature review identified previous cases of homozygosity for the same variant, but this is the first reported case of compound heterozygosity involving both a base deletion and a CNV. A review of five prior studies on <jats:italic>ZSWIM7<\/jats:italic> variants and infertility supports the conclusion that <jats:italic>ZSWIM7<\/jats:italic> is associated with infertility in both sexes. Our findings suggest that loss\u2010of\u2010function pathogenic variants in <jats:italic>ZSWIM7<\/jats:italic> negatively affect the formation and maintenance of male and female gonads.<\/jats:p>","DOI":"10.1002\/ajmg.a.64078","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T06:46:06Z","timestamp":1744872366000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Compound Heterozygous Variants in <scp><i>ZSWIM7<\/i><\/scp> Gene Linked to Infertility and Its Role in Gonadal Development"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-6417","authenticated-orcid":false,"given":"Denise M.","family":"Christofolini","sequence":"first","affiliation":[{"name":"Department of Collective Health, Genetics Division Centro Universit\u00e1rio FMABC  Santo Andr\u00e9 Brazil"},{"name":"Instituto Ideia F\u00e9rtil de Sa\u00fade Reprodutiva  Santo Andr\u00e9 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