دورية أكاديمية
أعرض في EDS

Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism.

التفاصيل البيبلوغرافية
العنوان: Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism.
المؤلفون: Pitteloud N; Department of Medicine and Harvard Reproductive Endocrine Science Centers, Massachusetts General Hospital, Boston, MA 02114, USA. npitteloud@partners.org, Zhang C, Pignatelli D, Li JD, Raivio T, Cole LW, Plummer L, Jacobson-Dickman EE, Mellon PL, Zhou QY, Crowley WF Jr
المصدر: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2007 Oct 30; Vol. 104 (44), pp. 17447-52. Date of Electronic Publication: 2007 Oct 24.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0027-8424 (Print) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : National Academy of Sciences
مواضيع طبية MeSH: Gastrointestinal Hormones/*metabolism , Hypogonadism/*metabolism , Hypogonadism/*pathology , Kallmann Syndrome/*metabolism , Kallmann Syndrome/*pathology , Neuropeptides/*metabolism, Animals ; Base Sequence ; Cell Movement ; Female ; Gastrointestinal Hormones/deficiency ; Gastrointestinal Hormones/genetics ; Gene Deletion ; Gene Expression Regulation ; Genotype ; Gonadotropin-Releasing Hormone/metabolism ; Humans ; Hypogonadism/genetics ; Kallmann Syndrome/genetics ; Male ; Mice ; Mice, Knockout ; Mutation/genetics ; Neurons/cytology ; Neurons/metabolism ; Neuropeptides/deficiency ; Neuropeptides/genetics ; Pedigree ; Phenotype ; Reproduction
مستخلص: Gonadotropin-releasing hormone (GnRH) deficiency in the human presents either as normosmic idiopathic hypogonadotropic hypogonadism (nIHH) or with anosmia [Kallmann syndrome (KS)]. To date, several loci have been identified to cause these disorders, but only 30% of cases exhibit mutations in known genes. Recently, murine studies have demonstrated a critical role of the prokineticin pathway in olfactory bulb morphogenesis and GnRH secretion. Therefore, we hypothesize that mutations in prokineticin 2 (PROK2) underlie some cases of KS in humans and that animals deficient in Prok2 would be hypogonadotropic. One hundred IHH probands (50 nIHH and 50 KS) with no known mutations were examined for mutations in the PROK2 gene. Mutant PROK2s were examined in functional studies, and the reproductive phenotype of the Prok2(-/-) mice was also investigated. Two brothers with KS and their sister with nIHH harbored a homozygous deletion in the PROK2 gene (p.[I55fsX1]+[I55fsX1]). Another asymptomatic brother was heterozygous for the deletion, whereas both parents (deceased) had normal reproductive histories. The identified deletion results in a truncated PROK2 protein of 27 amino acids (rather than 81 in its mature form) that lacks bioactivity. In addition, Prok2(-/-) mice with olfactory bulb defects exhibited disrupted GnRH neuron migration, resulting in a dramatic decrease in GnRH neuron population in the hypothalamus as well as hypogonadotropic hypogonadism. Homozygous loss-of-function PROK2 mutations cause both KS and nIHH.
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معلومات مُعتمدة: R01 HD015788 United States HD NICHD NIH HHS; U54 HD029164 United States HD NICHD NIH HHS; 5R01 HD015788 United States HD NICHD NIH HHS; R01 MH067753 United States MH NIMH NIH HHS; R01 HD020377 United States HD NICHD NIH HHS; R01 DK044838 United States DK NIDDK NIH HHS; DK044838 United States DK NIDDK NIH HHS; U54 HD028138 United States HD NICHD NIH HHS; P50 HD012303 United States HD NICHD NIH HHS; U54 HD012303 United States HD NICHD NIH HHS; U54 HD012303-280011 United States HD NICHD NIH HHS; MH067753 United States MH NIMH NIH HHS; R01 DK044838-19 United States DK NIDDK NIH HHS; R01 HD072754 United States HD NICHD NIH HHS; R01 DK044838-18 United States DK NIDDK NIH HHS; U54 HD012303-27 United States HD NICHD NIH HHS; U54 HD012303-28 United States HD NICHD NIH HHS; R37 HD020377 United States HD NICHD NIH HHS; HD020377 United States HD NICHD NIH HHS; U54 HD012303-270011 United States HD NICHD NIH HHS
المشرفين على المادة: 0 (Gastrointestinal Hormones)
0 (Neuropeptides)
0 (PROK2 protein, human)
0 (Prok2 protein, mouse)
33515-09-2 (Gonadotropin-Releasing Hormone)
تواريخ الأحداث: Date Created: 20071026 Date Completed: 20071227 Latest Revision: 20220309
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC2077276
DOI: 10.1073/pnas.0707173104
PMID: 17959774
قاعدة البيانات: MEDLINE
الوصف
تدمد:0027-8424
DOI:10.1073/pnas.0707173104