Homozygous mutation of KISS1 receptor () gene identified in a Chinese patient with congenital hypogonadotropic hypogonadism (CHH): case report and literature review.

OBJECTIVES

Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by a defect in the production, secretion or action of gonadotropin-releasing hormone. The absence of puberty and varying degrees of gonadotropic deficiency are common symptoms of this disorder. Heterogeneity exists in the clinical presentation of the different clinical subtypes and multiple genes have been implicated in CHH. A number of genetic defects have been identified as causes normosmic CHH, including mutations of , , , , and . Loss-of-function mutations in gene are a rare cause of normosmic CHH.

CASE PRESENTATION

We described an 11.5 years old Chinese patient who presented at birth with micropenis, microorchidia and bilateral cryptorchidism. Whole-exome sequencing was also performed and identified a homozygous mutation of gene, c.1010_1028del (p.V337Afs*82). The variant was predicted as "deleterious" and classified as "likely pathogenic". This variant has never been reported in patients with CHH. Furthermore, we summarized the clinical presentations and analyzed the phenotype-genotype correlation between CHH and mutations in previous reports.

CONCLUSIONS

This study details the clinical phenotypes and hormone levels of the patient and expands the spectrum of mutations in the gene associated with CHH.