Hypogonadotropic hypogonadism 8 with or without anosmia; HH8

Disease ID:468
Name:Hypogonadotropic hypogonadism 8 with or without anosmia; HH8
Associated with:1 target
Synonyms
Kallmann syndrome | Normosmic congenital hypogonadotropic hypogonadism
Database Links
Disease Ontology: DOID:3614
OMIM: 614837
Orphanet: ORPHA478, ORPHA432

Targets

kisspeptin receptor
Comments:  Splicing of exon 5 of the kisspeptin receptor results in a non-functional receptor and reduced FSH and LH secretion. This results in idiopathic hypogonadotrophic hypogonadism (IHH). The deletion of the splicing acceptor junction and part of exon 5 leads to an abnormal protein sequence downstream from residue 247. The deleted receptor is truncated within the third intracellular loop, thus lacking transmembrane domains 6 and 7 (de Roux et al., 2003).

Single nucleotide polymorphisms. Genetic linkage analysis identified a consanguineous family with IHH with a mutation in the kisspeptin receptor gene (L148S) and an unrelated proband with two mutations (R331X and X399R) resulting in the same phenotype (Seminara et al., 2003).

A C223R mutation in the 5th transmembrane helix and an R297L mutation in the 3rd extracellular loop have been found in human IHH patients. The former results in impaired receptor signalling and the latter results in a mild reduction in ligand-stimulated activity (Semple et al., 2005).
References:  1-3
Mutations:  kisspeptin receptor is associated with 6 mutation. Click here for details

Ligands

No ligand related data available for Hypogonadotropic hypogonadism 8 with or without anosmia; HH8

References

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1. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. (2003) Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A., 100: 10972-10976. [PMID:12944565]

2. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno Jr JS, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG et al.. (2003) The GPR54 gene as a regulator of puberty. N. Engl. J. Med., 349 (17): 1614-27. [PMID:14573733]

3. Semple RK, Achermann JC, Ellery J, Farooqi IS, Karet FE, Stanhope RG, O'Rahilly S, Aparicio SA. (2005) Two novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab., 90: 1849-1855. [PMID:15598687]