A Novel Double Mutation in the Luteinizing Hormone Receptor in a Kindred with Familial Leydig Cell Hypoplasia and Male Pseudohermaphroditism

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 T392I. The molecular effects of the mutations were inve...

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Bibliographic Details
Published in:Endocrine research 2005, Vol.31 (4), p.307-323
Main Authors: Pals-Rylaarsdam, Robin, Liu, Guoquan, Brickman, Wendy, Duranteau, Lise, Monroe, Jason, El-Awady, Mostafa K., Gad, Yehia Z., Shenker, Andrew
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Sequence
Animals
Cercopithecus aethiops
COS Cells
Cyclic AMP - biosynthesis
Cyclic AMP - metabolism
Disorders of Sex Development - genetics
Female
Human Growth Hormone - physiology
Humans
Leydig cell hypoplasia
Leydig Cells - pathology
Luteinizing hormone receptor
Male
Molecular Sequence Data
Mutation
Mutation, Missense
Pedigree
Pseudohermaphroditism
Receptors, LH - biosynthesis
Receptors, LH - genetics
Receptors, LH - metabolism
Restriction Mapping
Transfection
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Summary: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 T392I. 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.
ISSN:0743-5800
1532-4206
DOI:10.1080/07435800500430890