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McGlacken-Byrne SM, Le Quesne Stabej P, Del Valle I, et al. ZSWIM7 Is Associated With Human Female Meiosis and Familial Primary Ovarian Insufficiency. J Clin Endocrinol Metab. 2022;107(1):e254-e263doi: 10.1210/clinem/dgab597.
McGlacken-Byrne, S. M., Le Quesne Stabej, P., Del Valle, I., Ocaka, L., Gagunashvili, A., Crespo, B., Moreno, N., James, C., Bacchelli, C., Dattani, M. T., Williams, H. J., Kelberman, D., Achermann, J. C., & Conway, G. S. (2022). ZSWIM7 Is Associated With Human Female Meiosis and Familial Primary Ovarian Insufficiency. The Journal of clinical endocrinology and metabolism, 107(1), e254-e263. https://doi.org/10.1210/clinem/dgab597
McGlacken-Byrne, Sinéad M, et al. "ZSWIM7 Is Associated With Human Female Meiosis and Familial Primary Ovarian Insufficiency." The Journal of clinical endocrinology and metabolism vol. 107,1 (2022): e254-e263. doi: https://doi.org/10.1210/clinem/dgab597
McGlacken-Byrne SM, Le Quesne Stabej P, Del Valle I, Ocaka L, Gagunashvili A, Crespo B, Moreno N, James C, Bacchelli C, Dattani MT, Williams HJ, Kelberman D, Achermann JC, Conway GS. ZSWIM7 Is Associated With Human Female Meiosis and Familial Primary Ovarian Insufficiency. J Clin Endocrinol Metab. 2022 Jan 01;107(1):e254-e263. doi: 10.1210/clinem/dgab597. PMID: 34402903.
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J Clin Endocrinol Metab. 2022 Jan 01;107(1):e254-e263. doi: 10.1210/clinem/dgab597.

ZSWIM7 Is Associated With Human Female Meiosis and Familial Primary Ovarian Insufficiency.

The Journal of clinical endocrinology and metabolism

Sinéad M McGlacken-Byrne, Polona Le Quesne Stabej, Ignacio Del Valle, Louise Ocaka, Andrey Gagunashvili, Berta Crespo, Nadjeda Moreno, Chela James, Chiara Bacchelli, Mehul T Dattani, Hywel J Williams, Dan Kelberman, John C Achermann, Gerard S Conway

Affiliations

  1. Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
  2. Institute for Women's Health, University College London, London WC1N 1EH, UK.
  3. GOSgene, Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
  4. Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
  5. Developmental Biology and Cancer, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
  6. Division of Cancer and Genetics, Genetic and Genomic Medicine, Cardiff University, Cardiff CF14 4AY, UK.

PMID: 34402903 DOI: 10.1210/clinem/dgab597

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.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Keywords: NGS; delayed puberty; genetics; meiosis; ovary development; primary amenorrhea; primary ovarian insufficiency

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