(HealthDay News) – An inactivating mutation has been identified in the KISS1 gene in a consanguineous family, a mutation that results in failure of pubertal progression, according to a report published in the Feb. 16 issue of the New England Journal of Medicine.

A. Kemal Topaloglu, MD, from Cukurova University in Adana, Turkey, and colleagues describe an inactivating mutation in KISS1 in a consanguineous family to examine the role of loss-of-function mutations in human kisspeptin.

The investigators found that the proband had no breast development at age 14.9 years, and pelvic ultrasound revealed a hypoplastic uterus and ovaries lacking follicles. The proband had three sisters who also had no spontaneous breast development. Genome-wide single-nucleotide polymorphism analysis identified homozygous mutations in the coding sequence of KISS1 in all affected individuals, with all four homozygous for a cytosine-to-guanine change at nucleotide 345. Analysis of whole-exome sequencing data revealed that the only mutation to account for the phenotypes was the KISS1 mutation.

“In conclusion, we found that an inactivating mutation of KISS1 causes complete normosmic idiopathic hypogonadotropic hypogonadism in humans and would argue that kisspeptin signaling is a critical element in the human hypothalamic-pituitary-gonadal axis,” the authors write.

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