ZSWIM7 Is Associated With Human Female Meiosis and Familial Primary Ovarian Insufficiency
| Autor: | Nadjeda Moreno, Ignacio Del Valle Torres, Daniel Kelberman, Louise Ocaka, Chela James, Polona Le Quesne Stabej, Sinéad M. McGlacken-Byrne, Mehul T. Dattani, Gerard S. Conway, Andrey Gagunashvili, John C. Achermann, Berta Crespo, Chiara Bacchelli, Hywel Williams |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Gonad Adolescent Endocrinology Diabetes and Metabolism Clinical Biochemistry DNA Mutational Analysis Ovary Biology Primary Ovarian Insufficiency Biochemistry DNA sequencing Endocrinology Oogenesis Meiosis Loss of Function Mutation Internal medicine medicine Humans Point Mutation meiosis genetics RNA-Seq Child Online Only Articles Gene Amenorrhea Clinical Research Articles Genetics Fetus ovary development Biochemistry (medical) Zinc Fingers Phenotype delayed puberty Pedigree DNA-Binding Proteins medicine.anatomical_structure primary amenorrhea NGS Female Homologous recombination AcademicSubjects/MED00250 |
| Zdroj: | The Journal of Clinical Endocrinology and Metabolism |
| ISSN: | 1945-7197 0021-972X |
| Popis: | BackgroundPrimary 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.ObjectiveWe aimed to identify the genetic mechanism underlying early-onset POI in 2 sisters from a consanguineous pedigree.MethodsGenome 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.ResultsOnly 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 conclusionsDisruption 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|