Novel mutations of the LHCGR gene in two families with 46,XY DSD causing Leydig cell hypoplasia I

Purpose Leydig cell hypoplasia is a rare autosomal recessive 46,XY disorder of sexual development (DSD). It is caused by homozygous or compound heterozygous inactivating mutations in the human luteinizing hormone/chorionic gonadotropin hormone receptor (LHCGR) gene. In Leydig cell hypoplasia type I, patients are characterized by predominantly female external genitalia, which usually go unrecognized until the age of puberty. Methods This study reports three patients descending from two unrelated families. We performed clinical, hormonal, histopathological, molecular, and bioinformatics studies for the studied cases. Results All investigations suggested 46,XY DSD and Leydig cell hypoplasia. Molecular analysis showed two novel homozygous inactivating mutations (p.Glu148Ter and p.Leu104Pro) within the extracellular domain of the LHCGR gene. Conclusion Although the mutations of the LHCGR gene are distributed heterogeneously, without hotspot or recurrent mutations, about one fifth of the reported mutations worldwide have been detected in Arab patients. This is probably due to the high consanguinity rate in these populations, which increases the percentage of autosomal recessive disorders and the homozygous LHCGR gene mutations.