title: The genetic basis of female reproductive disorders: etiology and clinical testing.
abstract: With the advent of improved molecular biology techniques, the genetic basis of an increasing number of reproductive disorders has been elucidated. Mutations in at least 20 genes cause hypogonadotropic hypogonadism including Kallmann syndrome in about 35-40% of patients. The two most commonly involved genes are FGFR1 and CHD7. When combined pituitary hormone deficiency includes hypogonadotropic hypogonadism as a feature, PROP1 mutations are the most common of the six genes involved. For hypergonadotropic hypogonadism, mutations in 14 genes cause gonadal failure in 15% of affected females, most commonly in FMR1. In eugonadal disorders, activating FSHR mutations have been identified for spontaneous ovarian hyperstimulation syndrome; and WNT4 mutations have been described in mullerian aplasia. For other eugonadal disorders, such as endometriosis, polycystic ovary syndrome, and leiomyomata, specific germline gene mutations have not been identified, but some chromosomal regions are associated with the corresponding phenotype. Practical genetic testing is possible to perform in both hypogonadotropic and hypergonadotropic hypogonadism and spontaneous ovarian hyperstimulation syndrome. However, clinical testing for endometriosis, polycystic ovary syndrome, and leiomyomata is not currently practical for the clinician.
authors.affiliation: Section of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology, Institute of Molecular Medicine and Genetics, Neuroscience Program, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA. lalayman@gru.edu
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Layman
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000235:genetics; D000013:Congenital Abnormalities / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D012734:Disorders of Sex Development / Q000235:genetics; D004715:Endometriosis / Q000235:genetics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005831:Genital Diseases, Female / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D007889:Leiomyoma / Q000235:genetics; D008297:Male; D009095:Mullerian Ducts / Q000002:abnormalities; D016471:Ovarian Hyperstimulation Syndrome / Q000235:genetics; D010908:Pituitary Hormones, Anterior / Q000172:deficiency; D011085:Polycystic Ovary Syndrome / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D060528:Wnt4 Protein / Q000235:genetics
chemical_list: D004265:DNA Helicases; D004268:DNA-Binding Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D018398:Homeodomain Proteins; D010908:Pituitary Hormones, Anterior; D051496:Receptor, Fibroblast Growth Factor, Type 1; D060528:Wnt4 Protein; C497683:FMR1 protein, human; C102134:Prophet of Pit-1 protein; C555581:WNT4 protein, human; C496348:FGFR1 protein, human; C491434:CHD7 protein, human