Compound heterozygous mutations in the luteinizing hormone receptor signal peptide causing 46,XY disorder of sex development.

Compound heterozygous mutations in the luteinizing hormone receptor signal peptide causing 46,XY disorder of sex development. Eur J Endocrinol. 2019 Jun 01;: Authors: Potorac I, Trehan A, Szymanska K, Fudvoye J, Thiry A, Huhtaniemi IT, Daly AF, Beckers A, Parent AS, Rivero-Müller A Abstract Testosterone production by the fetal testis depends on a functional relationship between hCG and the LH/chorionic gonadotrophin receptor (LHCGR). Failure of the receptor to correctly respond to its ligand leads to impaired sexual differentiation in males. A phenotypically-female patient with pubertal delay, had a 46,XY karyotype and was diagnosed with 46X,Y disorder of sex development (DSD). Novel compound heterozygous LHCGR mutations were found in the signal peptide: a duplication p.L10_Q17dup of maternal origin, and a deletion (p.K12_L15del) and a p.L16Q missense mutation of paternal origin. cAMP production was very low for both the deletion and duplication mutations and was halved for the missense mutant. The duplication and missense mutations were both expressed intracellularly, but at very low levels at the cell membrane; they were most likely retained in the endoplasmic reticulum. The deletion mutant had a very limited intracellular expression, indicating impaired biosynthesis. There was reduced expression of all three mutants, which was most marked for the deletion mutation. There was also decreased protein expression of all three mutant r...
Source: European Journal of Endocrinology - Category: Endocrinology Authors: Tags: Eur J Endocrinol Source Type: research