Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
Nicolas de Roux,Emmanuelle Génin,Jean Claude Carel,Fumihiko Matsuda,Chaussain Jl,Edwin Milgrom +5 more
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TLDR
The present study shows that loss of function of GPR54 is a cause of IHH, and it identifies GPR 54 and possibly KiSS1 protein-derived peptide as playing a major and previously unsuspected role in the physiology of the gonadotropic axis.Abstract:
Hypogonadotropic hypogonadism is defined as a deficiency of the pituitary secretion of follicle-stimulating hormone and luteinizing hormone, which results in the impairment of pubertal maturation and of reproductive function. In the absence of pituitary or hypothalamic anatomical lesions and of anosmia (Kallmann syndrome), hypogonadotropic hypogonadism is referred to as isolated hypogonadotropic hypogonadism (IHH). A limited number of IHH cases are due to loss-of-function mutations of the gonadotropin-releasing hormone receptor. To identify additional gene defects leading to IHH, a large consanguineous family with five affected siblings and with a normal gonadotropin-releasing hormone receptor coding sequence was studied. Homozygosity whole-genome mapping allowed the localization of a new locus within the short arm of chromosome 19 (19p13). Sequencing of several genes localized within this region showed that all affected siblings of the family carried a homozygous deletion of 155 nucleotides in the GPR54 gene. This deletion encompassed the splicing acceptor site of intron 4-exon 5 junction and part of exon 5. The deletion was absent or present on only one allele in unaffected family members. GPR54 has been initially identified as an orphan G protein-coupled receptor with 40% homology to galanin receptors. Recently, a 54-aa peptide derived from the KiSS1 protein was identified as a ligand of GPR54. The present study shows that loss of function of GPR54 is a cause of IHH, and it identifies GPR54 and possibly KiSS1 protein-derived peptide as playing a major and previously unsuspected role in the physiology of the gonadotropic axis.read more
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References
More filters
Journal Article
Parametric and nonparametric linkage analysis: a unified multipoint approach.
TL;DR: It is shown that NPL is robust to uncertainty about mode of inheritance, is much more powerful than commonly used nonparametric methods, and loses little power relative to parametric linkage analysis, and appears to be the method of choice for pedigree studies of complex traits.
Journal ArticleDOI
A comprehensive genetic map of the human genome based on 5,264 microsatellites
Colette Dib,Sabine Fauré,Cécile Fizames,Delphine Samson,N. Drouot,Alain Vignal,P Millasseau,S Marc,Jamilé Hazan,Eric Seboun,Mark Lathrop,Gabor Gyapay,Jean Morissette,Jean Morissette,Jean Weissenbach +14 more
TL;DR: The last version of the Généthon human linkage map is reported, which consists of 5,264 short tandem repeat polymorphisms with a mean heterozygosity of 70%.
Journal ArticleDOI
The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54.
Masato Kotani,Michel Detheux,Ann Vandenbogaerde,David Communi,Jean-Marie Vanderwinden,Emmanuel Le Poul,Stéphane Brézillon,Richard Tyldesley,Nathalie Suarez-Huerta,Fabrice Vandeput,Cédric Blanpain,Serge N. Schiffmann,Gilbert Vassart,Marc Parmentier +13 more
TL;DR: Stimulation of oxytocin secretion after kisspeptin administration to rats confirmed this hypothesis that human GPR54 was highly expressed in placenta, pituitary, pancreas, and spinal cord, suggesting a role in the regulation of endocrine function.
Journal Article
Faster sequential genetic linkage computations.
TL;DR: A variety of algorithmic improvements are described, which synthesize biological principles with computer science techniques, to effectively restructure the time-consuming computations in genetic linkage analysis.
Journal ArticleDOI
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.
Tetsuya Ohtaki,Yasushi Shintani,Susumu Honda,Hirokazu Matsumoto,Akira Hori,Kimiko Kanehashi,Yasuko Terao,Satoshi Kumano,Yoshihiro Takatsu,Yasushi Masuda,Yoshihiro Ishibashi,Takuya Watanabe,Mari Asada,Takao Yamada,Masato Suenaga,Chieko Kitada,Satoshi Usuki,Tsutomu Kurokawa,Haruo Onda,Osamu Nishimura,Masahiko Fujino +20 more
TL;DR: It is shown that KiSS-1 encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which is isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and named ‘metastin’.
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