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

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          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.

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          Most cited references34

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          A second-generation linkage map of the human genome.

          A linkage map of the human genome has been constructed based on the segregation analysis of 814 newly characterized polymorphic loci containing short tracts of (C-A)n repeats in a panel of DNAs from eight large families. Statistical linkage analysis placed 813 of the markers into 23 linkage groups corresponding to the 22 autosomes and the X chromosome; 605 show a heterozygosity above 0.7 and 553 could be ordered with odds ratios above 1,000:1. The distance spanned corresponds to approximately 90% of the estimated length of the human genome.
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            • Record: found
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            Hormonal control of gene expression in the ovary.

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              A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty.

              Familial male precocious puberty (FMPP) is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern. Affected males generally exhibit signs of puberty by age 4. Testosterone production and Leydig cell hyperplasia occur in the context of prepubertal levels of luteinizing hormone (LH). The LH receptor is a member of the family of G-protein-coupled receptors, and we hypothesized that FMPP might be due to a mutant receptor that is activated in the presence of little or no agonist. A single A-->G base change that results in substitution of glycine for aspartate at position 578 in the sixth transmembrane helix of the LH receptor was found in affected individuals from eight different families. Linkage of the mutation to FMPP was supported by restriction-digest analysis. COS-7 cells expressing the mutant LH receptor exhibited markedly increased cyclic AMP production in the absence of agonist, suggesting that autonomous Leydig cell activity in FMPP is caused by a constitutively activated LH receptor.
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                Author and article information

                Journal
                Cell
                Cell
                Elsevier BV
                00928674
                September 1995
                September 1995
                : 82
                : 6
                : 959-968
                Article
                10.1016/0092-8674(95)90275-9
                7553856
                41b5f8f1-5df3-4136-b6cc-1b2d44be3eac
                © 1995

                https://www.elsevier.com/tdm/userlicense/1.0/

                https://www.elsevier.com/open-access/userlicense/1.0/

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