{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:35:51Z","timestamp":1790660151041,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFC2703800"],"award-info":[{"award-number":["2022YFC2703800"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32270658"],"award-info":[{"award-number":["32270658"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32288101"],"award-info":[{"award-number":["32288101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,10]]},"abstract":"<jats:p>\n                    Premature ovarian insufficiency (POI) is a complex reproductive disorder with a strong genetic component. The known POI causative genes currently account for only a small fraction of cases. In this study, we conducted whole-exome sequencing and identified a rare heterozygous missense variant in DNA helicase B (\n                    <jats:italic>HELB<\/jats:italic>\n                    ) (c.349G&gt;T, p.Asp117Tyr) in a Chinese family with POI and early menopause. To investigate the pathogenicity of this variant, a knockin mouse model carrying a heterozygous missense\n                    <jats:italic>Helb<\/jats:italic>\n                    variant (\n                    <jats:italic>Helb<\/jats:italic>\n                    <jats:sup>+\/D112Y<\/jats:sup>\n                    ) homologous to the human\n                    <jats:italic>HELB<\/jats:italic>\n                    c.349G&gt;T was constructed. The\n                    <jats:italic>Helb<\/jats:italic>\n                    -mutated female mice exhibited reduced litter sizes and prolonged interlitter intervals compared with wild-type mice after reaching 10 months of age, leading to a shortened reproductive lifespan. Consistently, aged\n                    <jats:italic>Helb<\/jats:italic>\n                    <jats:sup>+\/D112Y<\/jats:sup>\n                    females showed decreased ovarian weight and accelerated follicle depletion. Transcriptomic analysis of the ovaries from\n                    <jats:italic>Helb<\/jats:italic>\n                    -mutated mice revealed dysregulated expression of genes associated with impaired ovarian function and ovarian aging. Collectively, these findings in both humans and mice suggest that\n                    <jats:italic>HELB<\/jats:italic>\n                    is involved in maintaining ovarian function and regulating reproductive aging, highlighting the importance of\n                    <jats:italic>HELB<\/jats:italic>\n                    in female reproductive health.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.191122","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T19:00:41Z","timestamp":1762714841000},"source":"Crossref","is-referenced-by-count":3,"title":["Genetic variants in HELB contribute to premature ovarian insufficiency and early age of natural menopause"],"prefix":"10.1172","volume":"10","author":[{"given":"Yuncheng","family":"Pan","sequence":"first","affiliation":[{"name":"School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, 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