A novel missense homozygous inactivating mutation in the fourth transmembrane helix of the luteinizing hormone receptor in leydig cell hypoplasia

American Journal of Medical Genetics. Part a
Michael Yiu-Kwong LeungWai-Yee Chan

Abstract

Loss-of-function mutations/inactivating mutations of the human chorionic gonadotropin/luteinizing hormone receptor (hCG/LHR), a G-protein coupled receptor, lead to impaired Leydig cell differentiation. Leydig cell hypoplasia/agenesis/dysplasia (LCH) is one of the causes of male pseudohermaphroditism (MPH). We studied a 19-year-old MPH patient with female phenotype and 46,XY karyotype. Testicular histology and hormonal profile of the patient is typical of LCH. Nucleotide sequencing of exon 11 of hLHR identified a novel T1505C transversion mutation. The mutation is homozygous in the patient and is heterozygous in both parents. The single base mutation caused the substitution of a conserved leucine at 502 position to proline in transmembrane helix (TM) IV of the hLHR. This is the first LCH causing mutation identified in TM IV of the hLHR. Expression study of the mutated hLHR in human embryonic kidney (HEK)293 cells showed reduced cAMP production and ligand binding. Receptor trafficking was not affected by the mutation when the green fluorescence protein conjugated mutated receptor was expressed in HEK293 cells. The mutation caused inactivation of the hLHR and resulted in LCH in the patient.

References

Oct 28, 1976·The New England Journal of Medicine·F BerthezèneR Mornex
Mar 14, 2000·Archives of Medical Research·S M Wu, W Y Chan

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Citations

May 21, 2013·Human Reproduction Update·Britta TroppmannJörg Gromoll
Aug 27, 2005·Reproduction : the Official Journal of the Society for the Study of Fertility·Axel P N Themmen
Sep 29, 2018·Minerva ginecologica·Kamila SzymańskaAdolfo Rivero-Müller
May 20, 2006·Molecular Endocrinology·Michael Yiu-Kwong LeungWai-Yee Chan

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