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ZSWIM7 is associated with human female meiosis and familial primary ovarian insufficiency.

McGlacken-Byrne, SM; Le Quesne Stabej, P; Del Valle Torres, I; Ocaka, L; Gagunashvili, A; Crespo, B; Moreno, N; ... Conway, GS; + view all (2021) ZSWIM7 is associated with human female meiosis and familial primary ovarian insufficiency. The Journal of clinical endocrinology and metabolism 10.1210/clinem/dgab597. (In press). Green open access

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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 two sisters from a consanguineous pedigree. // Methods: Genome sequencing and variant filtering using an autosomal recessive model was performed in the two 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 (CS) 22/23, 9 weeks post conception (wpc), 11wpc, 15/16wpc, 19/20wpc) and in adult tissue. // Results: Only one homozygous variant co-segregating with the POI phenotype was found: a single nucleotide substitution in ZSWIM7, NM_001042697.2: c.173C>G; resulting in predicted loss-of-function p.(Ser58*). qRT-PCR demonstrated higher expression of ZSWIM7 in the 15/16wpc ovary compared to 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 and these findings expand the range of genes associated with POI in women.

Type: Article
Title: ZSWIM7 is associated with human female meiosis and familial primary ovarian insufficiency.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1210/clinem/dgab597
Publisher version: https://doi.org/10.1210/clinem/dgab597
Language: English
Additional information: © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10133387
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