Case Report

Novel Compound Heterozygous Variants in the LHCGR Gene in a Genetically Male Patient with Female External Genitalia


  • Mei Yan
  • Julaiti Dilihuma
  • Yanfei Luo
  • Baoerhan Reyilanmu
  • Yiping Shen
  • Maimaiti Mireguli

J Clin Res Pediatr Endocrinol 0;0(0):0-0 [e-Pub] PMID: 30444213


The LHCGR gene encodes a G-protein coupled receptor that plays a pivotal role in sexual differentiation in males, ovarian development in females, and in fertility via its interaction with luteinizing hormone (LH) and chorionic gonadotropin (CG). Inactive variants of the LHCGR gene cause Leydig cell hypoplasia (LCH), which is a rare disease and one of the causes of disorder of sexual differentiation (DSD) in males. The aim of this work is to study the clinical and molecular characteristics of a 2-year-9-month old patient with type 1 LCH.


Whole-exome sequencing was performed for the patient family, and variants in the LHCGR gene were validated by Sanger sequencing. Pathogenicity of the missense variant was evaluated by multiple in silico tools.


The Chinese patient, who exhibits DSD, has female external genitalia (normal labia majora and minora, external opening of urethra under the clitoris and blind-ended vagina) and bilateral testis tissues in the inguinal region. Genetic sequencing revealed compound heterozygous variants in the LHCGR gene in the patient, including a novel missense variant in exon 4 (c.349G>A, p.Gly117Arg) and a novel nonsense variant in exon 10 (c.878C>A, p.Ser293*). The missense variant is in the first leucine-rich repeat (LRR) domain of the LHCGR protein, which is predicted to affect ligand recognition and binding affinity and thus protein function.


The patient is molecularly and clinically diagnosed with type 1 LCH, which is caused by novel, compound heterozygous variants of the LHCGR gene. This report expanded the genotypic spectrum of LHCGR variants.

Keywords: Disorder of sexual differentiation (DSD), Leydig cell hypoplasia (LCH), LHCGR gene, novel variants