Homozygous FIGLA missense variant in two Japanese sisters with primary ovarian insufficiency: Case reports and literature review
Abstract Background FIGLA is a transcription factor gene which plays a critical role in folliculogenesis. Consistent with this, FIGLA variants have been identified in females with non‐syndromic primary ovarian insufficiency (POI) in both autosomal‐dominant and autosomal‐recessive forms. Case Descrip...
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2025-01-01
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| Series: | Reproductive Medicine and Biology |
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| Online Access: | https://doi.org/10.1002/rmb2.12635 |
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| author | Wataru Tanikawa Hirotomo Saitsu Yasuhiko Nakamura Yuichiro Shirafuta Yasuko Fujisawa Maki Fukami Norihiro Sugino Tsutomu Ogata |
| author_facet | Wataru Tanikawa Hirotomo Saitsu Yasuhiko Nakamura Yuichiro Shirafuta Yasuko Fujisawa Maki Fukami Norihiro Sugino Tsutomu Ogata |
| author_sort | Wataru Tanikawa |
| collection | DOAJ |
| description | Abstract Background FIGLA is a transcription factor gene which plays a critical role in folliculogenesis. Consistent with this, FIGLA variants have been identified in females with non‐syndromic primary ovarian insufficiency (POI) in both autosomal‐dominant and autosomal‐recessive forms. Case Description We encountered two Japanese sisters who had secondary or primary amenorrhea at 15 years of age. They were diagnosed as having non‐syndromic primary ovarian insufficiency (POI) with hypergonadotropic hypoestrogenism and markedly low serum anti‐Müllerian hormone values. Outcome Whole genome sequencing revealed a novel homozygous missense variant, NM_001004311.3:c.338A>G:p.(Tyr113Cys), in FIGLA essential for folliculogenesis in the two sisters. The parents were heterozygous for this variant, and the heterozygous mother had regular menses at 51 years of age. This variant was extremely rare in public databases, and was invariably assessed as deleterious by six prediction tools. Furthermore, the p.(Tyr113Cys)‐FIGLA protein was assessed as “pathogenic” or “likely pathogenic” by protein structural predictions, and was evaluated as “destabilizing” or “decrease stability” by protein stability predictions Conclusion The results, in conjunction with the data reported in the literature, imply that FIGLA variants account for a small but certain fraction of non‐syndromic POI, and pose a question as to the relevance of FIGLA variants to an autosomal dominant form of POI, although FIGLA variants have been identified in both autosomal dominant and autosomal recessive forms of non‐syndromic POI. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
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| series | Reproductive Medicine and Biology |
| spelling | doaj-art-03ca567b7e314bdb9222cfc67eea051b2025-08-20T06:16:47ZengWileyReproductive Medicine and Biology1445-57811447-05782025-01-01241n/an/a10.1002/rmb2.12635Homozygous FIGLA missense variant in two Japanese sisters with primary ovarian insufficiency: Case reports and literature reviewWataru Tanikawa0Hirotomo Saitsu1Yasuhiko Nakamura2Yuichiro Shirafuta3Yasuko Fujisawa4Maki Fukami5Norihiro Sugino6Tsutomu Ogata7Department of Pediatrics Hamamatsu University School of Medicine Hamamatsu JapanDepartment of Biochemistry Hamamatsu University School of Medicine Hamamatsu JapanDepartment of Obstetrics and Gynecology Yamaguchi Prefectural Grand Medical Center Hofu JapanDepartment of Obstetrics and Gynecology Yamaguchi University School of Medicine Ube JapanDepartment of Pediatrics Hamamatsu University School of Medicine Hamamatsu JapanDepartment of Molecular Endocrinology National Research Institute for Child Health and Development Tokyo JapanDepartment of Obstetrics and Gynecology Yamaguchi University School of Medicine Ube JapanDepartment of Pediatrics Hamamatsu University School of Medicine Hamamatsu JapanAbstract Background FIGLA is a transcription factor gene which plays a critical role in folliculogenesis. Consistent with this, FIGLA variants have been identified in females with non‐syndromic primary ovarian insufficiency (POI) in both autosomal‐dominant and autosomal‐recessive forms. Case Description We encountered two Japanese sisters who had secondary or primary amenorrhea at 15 years of age. They were diagnosed as having non‐syndromic primary ovarian insufficiency (POI) with hypergonadotropic hypoestrogenism and markedly low serum anti‐Müllerian hormone values. Outcome Whole genome sequencing revealed a novel homozygous missense variant, NM_001004311.3:c.338A>G:p.(Tyr113Cys), in FIGLA essential for folliculogenesis in the two sisters. The parents were heterozygous for this variant, and the heterozygous mother had regular menses at 51 years of age. This variant was extremely rare in public databases, and was invariably assessed as deleterious by six prediction tools. Furthermore, the p.(Tyr113Cys)‐FIGLA protein was assessed as “pathogenic” or “likely pathogenic” by protein structural predictions, and was evaluated as “destabilizing” or “decrease stability” by protein stability predictions Conclusion The results, in conjunction with the data reported in the literature, imply that FIGLA variants account for a small but certain fraction of non‐syndromic POI, and pose a question as to the relevance of FIGLA variants to an autosomal dominant form of POI, although FIGLA variants have been identified in both autosomal dominant and autosomal recessive forms of non‐syndromic POI.https://doi.org/10.1002/rmb2.12635disease‐causingFIGLAinheritanceprimary ovarian insufficiencywhole genome sequencing |
| spellingShingle | Wataru Tanikawa Hirotomo Saitsu Yasuhiko Nakamura Yuichiro Shirafuta Yasuko Fujisawa Maki Fukami Norihiro Sugino Tsutomu Ogata Homozygous FIGLA missense variant in two Japanese sisters with primary ovarian insufficiency: Case reports and literature review Reproductive Medicine and Biology disease‐causing FIGLA inheritance primary ovarian insufficiency whole genome sequencing |
| title | Homozygous FIGLA missense variant in two Japanese sisters with primary ovarian insufficiency: Case reports and literature review |
| title_full | Homozygous FIGLA missense variant in two Japanese sisters with primary ovarian insufficiency: Case reports and literature review |
| title_fullStr | Homozygous FIGLA missense variant in two Japanese sisters with primary ovarian insufficiency: Case reports and literature review |
| title_full_unstemmed | Homozygous FIGLA missense variant in two Japanese sisters with primary ovarian insufficiency: Case reports and literature review |
| title_short | Homozygous FIGLA missense variant in two Japanese sisters with primary ovarian insufficiency: Case reports and literature review |
| title_sort | homozygous figla missense variant in two japanese sisters with primary ovarian insufficiency case reports and literature review |
| topic | disease‐causing FIGLA inheritance primary ovarian insufficiency whole genome sequencing |
| url | https://doi.org/10.1002/rmb2.12635 |
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