title: A nonsense mutation of the human luteinizing hormone receptor gene in Leydig cell hypoplasia.
abstract: Leydig cell hypoplasia (LCH) is a form of male pseudohermaphroditism in which Leydig cell differentiation and testosterone production are impaired. This report describes the first case of a nonsense mutation (A1635C) in exon 11 of the human luteinizing hormone receptor (hLHR) gene in two sisters with LCH. This mutation causes loss of function of the receptor by introducing a stop codon at residue 545 in transmembrane helix 5 of the hLHR. Surface expression of the truncated hLHR (hLHR-t545) in human embryonic kidney cells stably transfected with cDNA encoding hLHR-t545 was diminished compared to the wild-type hLHR and hCG-induced cAMP accumulation was impaired. These results establish that single base mutations in exon 11 of the hLHR gene can produce inactivation as well as activation of the hLHR. Furthermore, they demonstrate that functional domains between transmembrane helix 5 and the C-terminal cytoplasmic tail of the hLHR are required for normal cell surface expression of the receptor and signal transduction.
authors.affiliation: Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: L
authors.initials: L
authors.lastname: Laue
authors.forename: S M
authors.initials: SM
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Kudo
authors.forename: A J
authors.initials: AJ
authors.lastname: Hsueh
authors.forename: G B
authors.initials: GB
authors.lastname: Cutler
authors.forename: J E
authors.initials: JE
authors.lastname: Griffin
authors.forename: J D
authors.initials: JD
authors.lastname: Wilson
authors.forename: C
authors.initials: C
authors.lastname: Brain
authors.forename: A C
authors.initials: AC
authors.lastname: Berry
authors.forename: D B
authors.initials: DB
authors.lastname: Grant
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000378:metabolism; D018389:Codon, Nonsense / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D012734:Disorders of Sex Development / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005091:Exons; D005260:Female; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D006063:Chorionic Gonadotropin; D018389:Codon, Nonsense; D017931:DNA Primers; D018076:DNA, Complementary; D011974:Receptors, LH; D000242:Cyclic AMP