title: Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure.
abstract: Hypergonadotropic ovarian dysgenesis (ODG) with normal karyotype is a heterogeneous condition that in some cases displays Mendelian recessive inheritance. By systematically searching for linkage in multiplex affected families, we mapped a locus for ODG to chromosome 2p. As the previously cloned follicle-stimulating hormone receptor (FSHR) gene had been assigned to 2p, we searched it for mutations. A C566T transition in exon 7 of FSHR predicting an Ala to Val substitution at residue 189 in the extracellular ligand-binding domain segregated perfectly with the disease phenotype. Expression of the gene in transfected cells demonstrated a dramatic reduction of binding capacity and signal transduction, but apparently normal ligand-binding affinity of the mutated receptor. We conclude that the mutation causes ODG in these families.
authors.affiliation: Department of Medical Genetics, University of Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Aittomäki
authors.forename: J L
authors.initials: JL
authors.lastname: Lucena
authors.forename: P
authors.initials: P
authors.lastname: Pakarinen
authors.forename: P
authors.initials: P
authors.lastname: Sistonen
authors.forename: J
authors.initials: J
authors.lastname: Tapanainen
authors.forename: J
authors.initials: J
authors.lastname: Gromoll
authors.forename: R
authors.initials: R
authors.lastname: Kaskikari
authors.forename: E M
authors.initials: EM
authors.lastname: Sankila
authors.forename: H
authors.initials: H
authors.lastname: Lehväslaiho
authors.forename: A R
authors.initials: AR
authors.lastname: Engel
authors.forename: E
authors.initials: E
authors.lastname: Nieschlag
authors.forename: I
authors.initials: I
authors.lastname: Huhtaniemi
authors.forename: A
authors.initials: A
authors.lastname: de la Chapelle
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured / Q000502:physiology; D002889:Chromosomes, Human, Pair 2; D004586:Electrophoresis; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015994:Incidence; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology*; D010375:Pedigree; D011110:Polymorphism, Genetic; D016649:Primary Ovarian Insufficiency / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D011962:Receptors, FSH / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D011962:Receptors, FSH