Cozette Claire, Pujalte Mathilde, Celton Noémie, Bosquet Dorian, Copin Henri, Cabry Rosalie, Garçon Loic, Benkhalifa Moncef, Scheffler Florence, Jedraszak Guillaume
Reproductive Medicine and Biology Department, CECOS of Picardy, Amiens University Hospital, 80000 Amiens, France.
Department of Constitutional Genetics, Amiens University Hospital, 80000 Amiens, France.
Genes (Basel). 2025 Feb 22;16(3):251. doi: 10.3390/genes16030251.
Premature ovarian insufficiency (POI), affecting 1% of women, is characterized by the loss of ovarian activity with amenorrhea or oligomenorrhea and increased gonadotropins occurring before the age of 40 years. Iatrogenic, autoimmune, and genetic causes are known to be involved in POI, but nearly 70% of all forms remain unexplained. Recent and new genetic analyses promote the identification of new candidate genes. The aim of this study was to evaluate the contribution of array-CGH and next-generation sequencing (NGS) in the diagnosis of POI. Twenty-eight idiopathic POI patients with primary or secondary amenorrhea underwent genetic screening by array-CGH and NGS using a custom capture design of 163 genes known or suspected to be involved in ovarian function. The clinical, biological, and ultrasound characteristics of the patients were also recorded. Four of the twenty-eight patients had primary amenorrhea (14.3%), and twenty-four (85.7%) had secondary amenorrhea, with an average age at diagnosis of 27.7. Eleven patients (39.3%) had a family history of POI. Our study identified a genetic anomaly in 16 of 28 patients (57.1%): one patient carried a causal copy number variation (CNV), eight patients carried a causal single nucleotide variation (SNV)/indel variation (28.6%), and seven other patients carried variants of uncertain significance. Our study was the first to combine genetic analyses by using both array-CGH and NGS in the same patients. It confirmed the usefulness of both analyses in the identification of pathogenic variations responsible for idiopathic POI. Early genetic diagnosis plays a major role in the management of complications and the screening of relatives.
卵巢早衰（POI）影响1%的女性，其特征是卵巢功能丧失，伴有闭经或月经过少，且促性腺激素在40岁之前升高。已知医源性、自身免疫性和遗传因素与POI有关，但所有类型中近70%仍无法解释。最近的新基因分析促进了新候选基因的识别。本研究的目的是评估比较基因组杂交芯片（array-CGH）和下一代测序（NGS）在POI诊断中的作用。28例原发性或继发性闭经的特发性POI患者通过array-CGH和NGS进行基因筛查，采用定制捕获设计，检测163个已知或怀疑与卵巢功能有关的基因。还记录了患者的临床、生物学和超声特征。28例患者中4例（14.3%）为原发性闭经，24例（85.7%）为继发性闭经，诊断时平均年龄为27.7岁。11例患者（39.3%）有POI家族史。我们的研究在28例患者中的16例（57.1%）中发现了基因异常：1例患者携带致病性拷贝数变异（CNV），8例患者携带致病性单核苷酸变异（SNV）/插入缺失变异（28.6%），其他7例患者携带意义未明的变异。我们的研究首次在同一患者中联合使用array-CGH和NGS进行基因分析。它证实了这两种分析方法在识别导致特发性POI的致病变异方面的有效性。早期基因诊断在并发症管理和亲属筛查中起着重要作用。
