Three Siblings with Idiopathic Hypogonadotropic Hypogonadism in a Nonconsanguineous Family: A Novel <i>KISS1R/GPR54</i> Loss-of-Function Mutation

Abstract

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare disease caused by defects in the secretion of gonadotropin releasing hormone (GnRH) or the action of GnRH on the pituitary gonadotrophes. KISS1R is one of the genes which, when mutated, cause IHH and mutations of this gene are responsible for about 2-5% of patients with normosmic IHH (NIHH). In this report, we present three siblings with NIHH due to a compound heterozygous KISS1R mutation. Genetic studies were carried out in the 14 year old index case with IHH and three siblings, two of whom were prepubertal. Genomic DNA was extracted from peripheral leukocytes and KISS1R gene was sequenced by using standard polymerase chain reaction amplification procedures. In molecular analysis of the index case, a compound heterozygous mutation was determined in KISS1R gene c.969C>A (p.Y323X) (known pathogenic) and c.170T>C (p.L57P) (novel). Mutation c.170T>C (p.L57P) was inherited from the mother while c.969C>A (p.Y323X) was inherited from the father. The same genotype was also found in two of the three siblings. A compound heterozygous mutation of the KISS1 gene, including one novel mutation, was found to cause NIHH and also incomplete puberty in a non-consanguineous family.

Impact of Circadian Disruption on Female Mice Reproductive Function

“…En parallèle un phénotype identique a été rapporté chez des souris présentant une délétion homozygote du gène GPR-54 (Seminara et al 2003) (Lapatto et al 2007)( Figure 10). Depuis, d'autres mutations de GPR-54 ont été décrites chez l'humain (Brioude et al 2013) (Francou et al 2016) (Nalbantoglu et al 2019) (Moalla et al 2019). De manière générale, les mutations sur le gène de GPR-54 seraient responsables de 2% des HHI (Francou et al 2016).…”

Identification of KISS1R gene mutations in disorders of non‐obstructive azoospermia in the northeast population of China

“…Mutations of this gene have been identified in less than 5% of patients with normosmic IHH . Up to now, at least 20 different mutations have been described in the literature, most of which were loss‐of‐function mutations and were found to have variable clinical manifestation . KISS1R mutations which have been reported to be associated with IHH include point mutations, insertion, deletion, missense mutation, acceptor splice site mutation, and compound heterozygous mutation .…”

Molecular Diagnosis of Kallmann Syndrome by Whole Exon Sequencing and Bioinformatic Approaches&nbsp;

“…The following were ltered from the data: population with a mutation frequency greater than 1%, sites in the dbSNP database, and nonsense mutation sites (intron regions, synonymous mutations, and other mutations that do not affect protein function). The FGFR1, FGF8 [6,7], GNRHR [8], IGSF10 [9], PROK2, PROKR2 [10,11], TAC3, TACR3 [12], DAX1 [13], NSMF [14,15], CHD7 [16], SOX2 [17], FEZF1 [18], HS6ST1 [19], SOX10 [20], SEMA3A [21], KISS1 [22], KISS1R [23], IL17RD [24], and WDR11 [25] genes were analyzed for identi cation of the relevant pathogenic sites. Published literature was search based on the sites selected by PUBMED.…”