A novel phenotype combining primary ovarian insufficiency growth retardation and pilomatricomas with MCM8 mutation

Context: Primary Ovarian insufficiency (POI) affects 1% of women under 40 years and leads most often to definitive infertility with adverse health outcomes. Very recently, genes involved in DNA repair have been shown to cause POI.

Objective: To identify the cause of a familial POI in a consanguineous Turkish family.

Design: Exome sequencing was performed in the proposita and her mother. Chromosomal breaks were studied in lymphoblastoid cell lines treated with Mitomycin (MMC).

Setting and patients: The proposita presented intra-uterine and post-natal growth retardation, multiple pilomatricomas in childhood and primary amenorrhea. She was treated with growth hormone (GH) from 14 to 18 years.

Results: We identified a novel nonsense mutation in exon 9 of the minichromosome maintenance complex component 8 gene (MCM8) NM_001281522.1: c.925C>T/p.R309* yielding a truncated protein devoid of the 531 C-terminal residues.

The mutation was homozygous in the daughter and heterozy...

Context: 原发性卵巢功能不全（Primary Ovarian Insufficiency, POI）在40岁以下女性中的患病率为1%，最常导致永久性不孕，并伴随多种不良健康结局。近期研究表明，参与DNA修复的基因可引发POI。
Objective: 本研究旨在明确一个近亲婚配土耳其家族中的家族性POI病因。
Design: 对先证者及其母亲开展外显子组测序；对经丝裂霉素（Mitomycin, MMC）处理的淋巴母细胞系进行染色体断裂分析。
Setting and patients: 先证者表现为宫内及产后生长迟缓、儿童期多发毛母质瘤，以及原发性闭经；其于14至18岁期间接受生长激素（Growth Hormone, GH）治疗。
Results: 本研究在微染色体维持复合物组件8基因（minichromosome maintenance complex component 8, MCM8）NM_001281522.1的第9外显子中发现一种新型无义突变：c.925C>T/p.R309*，该突变可产生缺失531个C端残基的截短型蛋白质。该突变在女儿体内为纯合突变，在杂合……