Insights into the coexistence of two mutations in the same LHCGR gene locus causing severe Leydig cell hypoplasia.

BACKGROUND Leydig cell hypoplasia is a rare autosomal recessive condition that interferes with the normal development of male external genitalia in 46,XY individuals. It is mediated by mutations in the lutropin/choriogonadotropin receptor gene, resulting in the impairment of either the binding of hormone or signal transduction. OBJECTIVE/DESIGN We report a 32-year-old female patient with severe Leydig cell hypoplasia due to a novel homozygote nonsense mutation in exon 10 (c.907C>T, p.Gln303Ter) of the lutropin/choriogonadotropin receptor gene. Interestingly, a second mutation was found (c.935A>G, p.Asn312Ser) downstream of the disruption of the gene sequence. CONCLUSIONS This case report demonstrates the coexistence of a novel homozygote nonsense mutation with a second mutation in the same hormone binding domain, expanding the genotypic spectrum of lutropin-choriogonadotropic hormone receptor gene mutations. The first diagnosis of this mutation in an adult 46,XY female patient from Morocco underlines the importance of thorough clinical and genetic examination, not only in pre- and post-pubertal children but also in adults originating from conservative socio-cultural backgrounds.