{"id":280,"title":"Etiological Spectrum of Primary Ovarian Insufficiency in a Group of Children and Adolescents: A Tertiary Single-Center Experience","title_zh":"儿童与青少年原发性卵巢功能不全的病因谱：单中心三级医院经验","url":"https://pubmed.ncbi.nlm.nih.gov/42988313","doi":"10.1016/j.jpag.2026.11.001","pmid":"42988313","journal":"J Pediatr Adolesc Gynecol","kind":"paper","lang":"en","published_at":"2026-11-05T00:00:00+00:00","fetched_at":"2026-11-08T03:44:04+00:00","authors":["Karataş MÇ","Köprülü Ö","Cinleti T","Kaya ÖÖ","Acar S","Şimşek FY","Yalabık F","Erdoğan KM","Karapınar TH","Erbaş İM","Nalbantoğlu Ö","Korkmaz HA","Özkan B"],"primary_topic":"repro-endo","topics":[{"slug":"repro-endo","score":6.0,"hits":["amenorrhea","poi","primary ovarian insufficiency"]},{"slug":"oocyte","score":4.0,"hits":["ovarian"]},{"slug":"fertility-preservation","score":1.0,"hits":["gonadotoxic"]},{"slug":"repro-tox","score":1.0,"hits":["gonadotoxic"]}],"topic_score":6.0,"preference_score":0.0,"preference_labels":[],"llm_score":63.0,"final_score":63.0,"score_dims":{"novelty":60,"rigor":52,"impact":55,"relevance":78,"translation":62},"recommend_reason":"系统呈现了儿童青少年46,XX型POI的病因构成与NGS诊断收益，对生殖内分泌与遗传咨询有直接参考价值，并提示MCM9奠基者效应；但为小样本单中心回顾性研究、无功能验证，证据强度有限，可作为浏览与病例对照参考。","keywords":["原发性卵巢功能不全","46,XX","儿童青少年","二代测序","MCM9","医源性卵巢损伤"],"selected":1,"story_id":48,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-endo-genetics","source_name":"PubMed · 生殖内分泌/遗传/保存","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":null,"journal_tier":"unknown","journal_if":null,"is_mock":false,"summary_zh":"该研究回顾性分析了单中心25例18岁前确诊的原发性卵巢功能不全（POI）患儿与青少年，中位诊断年龄14.83岁。首发表现以原发闭经最常见（44%），其次为慢性病内分泌监测中发现（24%）、矮小（20%）与继发闭经（12%）。56%的患者检出遗传病因，变异涉及MCM9、HAX1、TALDO1、HFM1与MTRFR（C12orf65），其中MCM9与HAX1变异者家族聚集明显；医源性POI见于既往接受性腺毒性化疗、放疗或造血干细胞移植前预处理者。作者认为靶向NGS应纳入常规诊疗，同一MCM9变异在无关家系中反复出现提示可能存在奠基者效应。样本量小、缺乏功能验证，结论需更大队列验证。","summary":"OBJECTIVE: Primary ovarian insufficiency (POI) with a 46,XX karyotype is rare in pediatric and adolescent populations. It is a heterogeneous condition with important implications for pubertal development, fertility potential, genetic counseling, and long-term health. This study aimed to characterize the clinical, genetic, and etiological spectrum of pediatric and adolescent POI and to evaluate the diagnostic contribution of genetic testing. METHODS: We retrospectively analyzed pediatric and adolescent patients diagnosed with POI before 18 years of age. Demographic characteristics, presenting features, auxological data, hormonal profiles, imaging findings, molecular investigations, treatment-related exposures, and etiological classifications were analyzed. RESULTS: Twenty-five patients were included. The median age at diagnosis was 14.83 years (interquartile range [IQR]: 11.81-15.71). Primary amenorrhea was the most common presentation, observed in 44% of patients, followed by diagnosis during endocrine surveillance for chronic diseases in 24%, short stature in 20%, and secondary amenorrhea in 12%. Genetic etiologies were identified in 56% of patients, with variants detected in MCM9, HAX1, TALDO1, HFM1, and MTRFR (C12orf65). Familial clustering was particularly prominent among patients with MCM9 and HAX1 variants. Iatrogenic POI occurred in patients previously exposed to gonadotoxic chemotherapy, radiotherapy, or gonadotoxic conditioning regimens administered before hematopoietic stem cell transplantation (HSCT). CONCLUSIONS: In this study, we present the clinical characteristics of pediatric and adolescent patients with POI, including different etiologies and phenotypic presentations. Our findings underscore the value of targeted Next-Generation Sequencing (NGS) analysis in routine clinical practice. Moreover, the recurrent identification of the same MCM9 variant in unrelated families raises the possibility of a founder effect.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}