Carey A H, Chan K L, Short F, White D, Williamson R, Franks S
Department of Obstetrics and Gynaecology, St Mary's Hospital Medical School, Imperial College of Science Technology and Medicine, London, UK.
Clin Endocrinol (Oxf). 1993 Jun;38(6):653-8. doi: 10.1111/j.1365-2265.1993.tb02150.x.
Polycystic ovary syndrome is one of the most common endocrine disorders but its aetiology remains unknown. It is highly prevalent within families, suggesting a genetic basic for the syndrome, but the mode of inheritance is unclear. The purpose of this study was to determine the mode of inheritance of polycystic ovary syndrome, within the families of affected individuals, by classic segregation analysis.
All first degree relatives of affected individuals were screened for the presence or absence of polycystic ovaries in post-menarchal-premenopausal women and early onset male pattern baldness (MPB) in the males. In extended pedigrees, assignment of affected status in post-menopausal women was made by consideration of the clinical history alone.
Fourteen women (probands), presenting with a variety of clinical symptoms, were identified sequentially as having polycystic ovaries (PCO) by ultrasound scan. They were examined in detail to determine their family structure, clinical and endocrine status. Ten families were found to have sufficient members for further study.
All family members had their body mass index calculated, their degree of hirsutism assessed using the Ferriman and Gallwey score and serum levels of gonadotrophins (FSH and LH), testosterone, prolactin and 17 alpha-hydroxyprogesterone measured by radioimmunoassay. A careful reproductive history was taken for each woman and any menstrual disturbance was noted. Obese probands had their glucose and insulin response to a standard 75-g oral glucose tolerance test determined. Each male family member was also assessed for the degree and time of onset of balding.
First degree female relatives of affected individuals had a 51% chance of being affected. Early onset male pattern baldness (MPB) was found to be an accurate phenotype for obligate male carriers. Each family showed autosomal dominant inheritance for PCO with greater than 90% penetrance.
We postulate that PCO and male pattern baldness are caused by alleles of the same gene which affect androgen production or action. The different frequencies of PCO and male pattern baldness arise from differing thresholds for phenotypic expression in females and males respectively. The modifying effects of other genes is the most likely explanation of the somewhat variable phenotype.
多囊卵巢综合征是最常见的内分泌紊乱疾病之一，但其病因仍不清楚。该综合征在家族中具有高度普遍性，提示其存在遗传基础，但遗传模式尚不清楚。本研究的目的是通过经典的分离分析确定多囊卵巢综合征在受累个体家族中的遗传模式。
对受累个体的所有一级亲属进行筛查，检查绝经后至绝经前女性是否存在多囊卵巢，男性是否有早发性男性型秃发（MPB）。在扩展家系中，仅根据临床病史确定绝经后女性的受累状态。
通过超声扫描依次确定14名出现各种临床症状的女性（先证者）患有多囊卵巢（PCO）。对她们进行详细检查以确定其家族结构、临床和内分泌状况。发现有10个家族有足够的成员进行进一步研究。
计算所有家庭成员的体重指数，使用费里曼和高尔韦评分评估多毛症程度，通过放射免疫测定法测量促性腺激素（FSH和LH）、睾酮、催乳素和17α-羟孕酮的血清水平。为每位女性详细记录生殖史并记录任何月经紊乱情况。肥胖的先证者进行标准75克口服葡萄糖耐量试验，测定其血糖和胰岛素反应。对每个男性家庭成员也评估秃发的程度和开始时间。
受累个体的一级女性亲属有51%的患病几率。早发性男性型秃发（MPB）被发现是确定男性携带者的准确表型。每个家族的PCO均显示常染色体显性遗传，外显率大于90%。
我们推测PCO和男性型秃发是由影响雄激素产生或作用的同一基因的等位基因引起的。PCO和男性型秃发的不同发生率分别源于女性和男性表型表达的不同阈值。其他基因的修饰作用最有可能解释这种有点多变的表型。
