Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Its sequelae impact on most major health issues facing women, including diabetes, hypertension, cardiovascular disease and gynecological cancers. Despite extensive research, its etiology is unknown, and no consensus exists for its definition other than hyperandrogenic chronic anovulation. Previous studies have shown a strong familial tendency for PCOS. Though an autosomal pattern of inheritance seems probable, most studies have been inadequate. Other disorder which can produce phenocopies have not been eliminated. Additionally the phenotype of males and females of non-reproductive age has never been thoroughly established. We plan to intensively study a few large three generation kindreds of PCOS to reduce genetic heterogeneity. A normative data base will be established for age, weight, and ethnicity matched controls.
Our specific aims are to fully phenotypic previously identified kindreds of familial PCOS for clinical, biometric, and biochemical abnormalities. These will include historical characteristics, physical exam findings including ultrasound exam, reproductive hormone profiles, and assessment of insulin resistance. All available pedigree members, male and female will be phenotyped. The search is ultimately for a clinical marker or constellation of markers that are specific for the kindred as well as document the full range of metabolic abnormalities from a representative kindred. Segregation analysis of each of these phenotypes in isolation or in combination will determine the most predictable mode of inheritance. In the process we will assemble a DNA bank on complete PCOS pedigrees for genetic studies. We will then perform linkage analysis with regularly spaced polymorphic genetic marker to map a disease locus. We will begin with a rough survey of the genome using markers spaced at 20CM and refine it to higher resolution markers as necessary. Identifying a disease locus would ease identification of the disease gene. Ultimately such a genetic marker would be useful in identifying women at risk for developing PCOS prior to onset of complications. Medical resources could then be focused on preventing such complications.
| Legro, R S; Spielman, R; Urbanek, M et al. (1998) Phenotype and genotype in polycystic ovary syndrome. Recent Prog Horm Res 53:217-56 |
