{"doi":"10.1210/clinem/dgab597","title":"<i>ZSWIM7</i>Is Associated With Human Female Meiosis and Familial Primary Ovarian Insufficiency","abstract":"BACKGROUND: Primary ovarian insufficiency (POI) affects 1% of women and is associated with significant medical consequences. A genetic cause for POI can be found in up to 30% of women, elucidating key roles for these genes in human ovary development. OBJECTIVE: We aimed to identify the genetic mechanism underlying early-onset POI in 2 sisters from a consanguineous pedigree. METHODS: Genome sequencing and variant filtering using an autosomal recessive model was performed in the 2 affected sisters and their unaffected family members. Quantitative reverse transcriptase PCR (qRT-PCR) and RNA sequencing were used to study the expression of key genes at critical stages of human fetal gonad development (Carnegie Stage 22/23, 9 weeks post conception (wpc), 11 wpc, 15/16 wpc, 19/20 wpc) and in adult tissue. RESULTS: Only 1 homozygous variant cosegregating with the POI phenotype was found: a single nucleotide substitution in zinc finger SWIM-type containing 7 (ZSWIM7), NM_001042697.2: c.173C > G; resulting in predicted loss-of-function p.(Ser58*). qRT-PCR demonstrated higher expression of ZSWIM7 in the 15/16 wpc ovary compared with testis, corresponding to peak meiosis in the fetal ovary. RNA sequencing of fetal gonad samples showed that ZSWIM7 has a similar temporal expression profile in the developing ovary to other homologous recombination genes. MAIN CONCLUSIONS: Disruption of ZSWIM7 is associated with POI in humans. ZSWIM7 is likely to be important for human homologous recombination; these findings expand the range of genes associated with POI in women.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":159067,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9098,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":669242,"name":"Polona Le Quesne Stabej","orcid":"0000-0002-9436-5857","position":1,"is_corresponding":false},{"id":669243,"name":"Ignacio del Valle","orcid":"0000-0003-2595-3652","position":2,"is_corresponding":false},{"id":670063,"name":"Louise Ocaka","orcid":null,"position":3,"is_corresponding":false},{"id":670064,"name":"Andrey Gagunashvili","orcid":null,"position":4,"is_corresponding":false},{"id":669244,"name":"Berta Crespo","orcid":"0000-0003-0006-009X","position":5,"is_corresponding":false},{"id":669245,"name":"Nadjeda Moreno","orcid":"0009-0001-6385-2257","position":6,"is_corresponding":false},{"id":554668,"name":"Chela James","orcid":"0000-0003-3996-0909","position":7,"is_corresponding":false},{"id":670065,"name":"Chiara Bacchelli","orcid":null,"position":8,"is_corresponding":false},{"id":669246,"name":"Mehul Dattani","orcid":"0000-0002-0365-5809","position":9,"is_corresponding":false},{"id":33079,"name":"Hywel Williams","orcid":"0000-0001-7758-0312","position":10,"is_corresponding":false},{"id":542667,"name":"Daniel Kelberman","orcid":"0000-0003-0583-5237","position":11,"is_corresponding":false},{"id":669247,"name":"John C. Achermann","orcid":"0000-0001-8787-6272","position":12,"is_corresponding":false},{"id":669248,"name":"Gerard S. Conway","orcid":"0000-0002-3346-5029","position":13,"is_corresponding":false},{"id":669241,"name":"Sinead McGlacken‐Byrne","orcid":"0000-0002-4289-0852","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-18T23:44:35.165422Z","pmid":"34402903","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}