Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure

Cell. 1995 Sep 22;82(6):959-68. doi: 10.1016/0092-8674(95)90275-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cells, Cultured / physiology
  • Chromosomes, Human, Pair 2
  • Electrophoresis
  • Family Health
  • Female
  • Genetic Linkage
  • Genetic Testing
  • Haplotypes / genetics
  • Humans
  • Incidence
  • Molecular Sequence Data
  • Mutation / physiology*
  • Pedigree
  • Polymorphism, Genetic
  • Primary Ovarian Insufficiency / epidemiology
  • Primary Ovarian Insufficiency / etiology*
  • Primary Ovarian Insufficiency / genetics*
  • Receptors, FSH / genetics*
  • Sequence Analysis, DNA


  • Receptors, FSH