A novel variant luteinizing hormone receptor in the first transmembrane helix of two homozygous Iranian patients: case report

Abstract

Abstract Background Leydig cell hypoplasia (LCH) is a rare autosomal recessive endocrine syndrome that affects the normal development of male external genitalia in 46, XY individuals and is one of the causes of disorder of sexual differentiation (DSD) in males. The responsible gene of LCH is LHCGR which is located on the chromosome 2 and its various mutations lead to different degrees of the disease ranging from micropenis to complete XY DSD. Case presentation In this study, we have investigated the clinical presentation and molecular findings of two siblings with complete male LCH and XY DSD. This is the first detailed report of individuals with LCH from Iran. It aimed to study the molecular and clinical characteristics of two sisters with type 1 LCH. Whole exome sequencing was used for these patients to find the underlying genetic cause of the disease. Our Iranian DSD patients had external genitalia (normal labia major and minor, the external opening of the urethra beneath the clitoris) and bilateral testicular tissues in the inguinal region, which were removed by surgical exploration. Conclusions Genetic sequencing showed the homozygous variants of the LHCGR gene in the patients, a novel duplication variant in exon 11, c.1091dupT -or pLeu365Profs*5. This mutation is described as likely pathogenic. We think that this case report can widen the genotypic spectrum of the LHCGR variants. Moreover, this study emphasizes the significant rule of Whole Exome Sequencing in differentiating various causes of disorder of sexual differentiation.

Keywords

• Leydig cell hypoplasia
• Disorder of sexual differentiation
• LHCGR gene
• Novel variants