ArticlePloS one2013
Two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in KISS1R (KISS1 receptor): clinical evaluation and molecular characterization of a novel mutation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Tooth agenesis and orofacial clefting: genetic brothers in arms?Human genetics · 2016Pooled it
- Identification of a novel KISS1R (GPR54) gene variant (c.505+2T>G) in a patient with congenital hypogonadotropic hypogonadism: A case report and literature review.Experimental and therapeutic medicine · 2026Article
- Arcuate Nucleus of the Hypothalamus: Anatomy, Physiology, and Diseases.Experimental neurobiology · 2023Review
- Metabolic actions of kisspeptin signaling: Effects on body weight, energy expenditure, and feeding.Pharmacology & therapeutics · 2022Review
- The KiSS-1/GPR54 system: Essential roles in physiological homeostasis and cancer biology.Genes & diseases · 2022Review
- AGenes · 2019Article
- Nonstop mutation in the Kisspeptin 1 receptor (KISS1R) gene causes normosmic congenital hypogonadotropic hypogonadism.Journal of assisted reproduction and genetics · 2019Article
- An Isolated Hypogonadotropic Hypogonadism due to a L102P Inactivating Mutation of KISS1R/GPR54 in a Large Family.Case reports in pediatrics · 2019Article
- Changes in the Responsiveness of the Hypothalamic-Pituitary-Gonadal Axis to Kisspeptin-10 Administration during Pubertal Transition in Boys.International journal of endocrinology · 2018Article
- Computational Analysis of Missense Variants of G Protein-Coupled Receptors Involved in the Neuroendocrine Regulation of Reproduction.Neuroendocrinology · 2016Article
- The genetics of human infertility by functional interrogation of SNPs in mice.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders.Endocrinology and metabolism (Seoul, Korea) · 2015Review
- A Multi-Oscillatory Circadian System Times Female Reproduction.Frontiers in endocrinology · 2015Review
- "Been hit twice": a novel bi-allelic heterozygous mutation in LHCGR.Journal of assisted reproduction and genetics · 2014Article
- Reproduction, smell, and neurodevelopmental disorders: genetic defects in different hypogonadotropic hypogonadal syndromes.Frontiers in endocrinology · 2014Review
- Central hypogonadotropic hypogonadism: genetic complexity of a complex disease.International journal of endocrinology · 2014Review
- Development of a methodology for and assessment of pulsatile luteinizing hormone secretion in juvenile and adult male mice.Endocrinology · 2013Article
- Use of genetic models of idiopathic hypogonadotrophic hypogonadism in mice and men to understand the mechanisms of disease.Experimental physiology · 2013Review
- Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
contextKISS1R mutations have been reported in few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110).
objectiveTo describe in detail nCHH patients with biallelic KISS1R mutations belonging to 2 unrelated families, and to functionally characterize a novel KISS1R mutation.
resultsAn original mutant, p.Tyr313His, was found in the homozygous state in 3 affected kindred (2 females and 1 male) from a consanguineous Portuguese family. This mutation, located in the seventh transmembrane domain, affects a highly conserved amino acid, perturbs the conformation of the transmembrane segment, and impairs MAP kinase signaling and intracellular calcium release. In the second family, a French Caucasian male patient with nCHH was found to carry two recurrent mutations in the compound heterozygous state (p.Leu102Pro/Stop399Arg). In this man, pulsatile GnRH (Gonadotropin Releasing Hormone) administration restored pulsatile LH (Luteinizing Hormone) secretion and testicular hormone secretion. Later, long-term combined gonadotropin therapy induced spermatogenesis, enabling 3 successive pregnancies that resulted in 2 miscarriages and the birth of a healthy boy.
conclusionWe show that a novel loss-of-function mutation (p.Tyr313His) in the KISS1R gene can cause familial nCHH, revealing the crucial role of this amino acid in KISS1R function. The observed restoration of gonadotropin secretion by exogenous GnRH administration further supports, in humans, the hypothalamic origin of the gonadotropin deficiency in this genetic form of nCHH.
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