ClinVar

Laue et al. (1995) identified a cys545-to-ter mutation in exon 11 of the LHCGR gene in 2 46,XY sibs with male pseudohermaphroditism (238320). The mutation was an A-to-C transversion at nucleotide 1635 which caused loss of function of the receptor by introducing a stop codon at residue 545 in transmembrane helix 5 of the luteinizing hormone receptor. Surface expression of the truncated gene product in human embryonic kidney cells stably transfected with cDNA encoding the mutant protein was diminished compared to the wildtype gene, and hCG-induced cAMP accumulation was impaired. The mutation in the 2 sibs was present also in the normal father and was not present in the mother. The finding excludes the possibility of a dominant-negative mutation in the sisters and suggests that they are compound heterozygotes, the mutation inherited from the mother not being identified. The results of Laue et al. (1995) indicated that functional domains between transmembrane helix 5 and the C-terminal cytoplasmic tail of the gene are required for normal cell surface expression of the receptor and signal transduction. In the family reported by Laue et al. (1995), Wu et al. (1998) identified a loss of function mutation in the mother (152790.0021).