title: A novel double mutation in the luteinizing hormone receptor in a kindred with familial Leydig cell hypoplasia and male pseudohermaphroditism.
abstract: We report a novel mutant of the luteinizing hormone receptor (LHR) in a case of familial Leydig cell hypoplasia and pseudohermaphrotidism. The proband was homozygous for two missense mutations, T1121C and C1175T, causing substitutions I374T and T3921. The molecular effects of the mutations were investigated by heterologous expression of the WT LHR, the double mutant LHR, or receptors with either the I374T or the T392I mutation, and measuring hormone binding and cAMP signaling. All mutant LHRs exhibited severe defects, including loss of ligand binding and cAMP production. Immunoblots showed little difference in protein levels between the WT and mutant receptors.
authors.affiliation: Department of Pediatrics, Northwestern University Medical School and Children's Memorial Institute for Education and Research, Chicago, Illinois, USA. rrylaarsdam@trnty.edu
authors.forename: Robin
authors.initials: R
authors.lastname: Pals-Rylaarsdam
authors.forename: Guoquan
authors.initials: G
authors.lastname: Liu
authors.forename: Wendy
authors.initials: W
authors.lastname: Brickman
authors.forename: Lise
authors.initials: L
authors.lastname: Duranteau
authors.forename: Joson
authors.initials: J
authors.lastname: Monroe
authors.forename: Mostafa K
authors.initials: MK
authors.lastname: El-Awady
authors.forename: Yehia Z
authors.initials: YZ
authors.lastname: Gad
authors.forename: Andrew
authors.initials: A
authors.lastname: Shenker
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D012734:Disorders of Sex Development / Q000235:genetics*; D005260:Female; D019382:Human Growth Hormone / Q000502:physiology; D006801:Humans; D007985:Leydig Cells / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D011974:Receptors, LH / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D015183:Restriction Mapping; D014162:Transfection
chemical_list: D011974:Receptors, LH; D019382:Human Growth Hormone; D000242:Cyclic AMP