GnRH-deficient phenotypes in humans and mice with heterozygous variants in KISS1/Kiss1.

ABSTRACT:

Context

KISS1 is a candidate gene for GnRH deficiency.

Objective

Our objective was to identify deleterious mutations in KISS1.

Patients and methods

DNA sequencing and assessment of the effects of rare sequence variants (RSV) were conducted in 1025 probands with GnRH-deficient conditions.

Results

Fifteen probands harbored 10 heterozygous RSV in KISS1 seen in less than 1% of control subjects. Of the variants that reside within the mature kisspeptin peptide, p.F117L (but not p.S77I, p.Q82K, p.H90D, or p.P110T) reduces inositol phosphate generation. Of the variants that lie within the coding region but outside the mature peptide, p.G35S and p.C53R (but not p.A129V) are predicted in silico to be deleterious. Of the variants that lie outside the coding region, one (g

SUBMITTER: Chan YM 

PROVIDER: S-EPMC3205899 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature