Case Report

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


  • Ozlem Nalbantoglu
  • Gulcin Arslan
  • Ozge Koprulu
  • Filiz Hazan
  • Semra Gursoy
  • Behzat Ozkan

Received Date: 30.11.2018 Accepted Date: 27.02.2019 J Clin Res Pediatr Endocrinol 0;0(0):0-0 [e-Pub] PMID: 30905142


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, 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 aim to present three siblings who have 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 have incomplete puberty.


Genomic DNA was extracted from peripheral leukocytes and KISS1R gene was sequenced by using standard PCR 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.9C>A (p.Y323X) was inherited from the father. Also the same genotype was found in two of the three siblings.


A compound heterozygous mutation of KISS1 gene causes normosmic idiopathic hypogonadotropic hypogonadism and also incomplete puberty in a non- consanguineous family.

Keywords: Kisspeptin, KISS1R, hypogonadotropic hypogonadism, delayed puberty