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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorMARUI, Suemi
dc.contributor.authorTRARBACH, Ericka B.
dc.contributor.authorBOGUSZEWSKI, Margaret C. S.
dc.contributor.authorFRANCA, Marcela M.
dc.contributor.authorJORGE, Alexander A. L.
dc.contributor.authorINOUE, Hiroshi
dc.contributor.authorNISHI, Mirian Y.
dc.contributor.authorLACERDA FILHO, Luiz de
dc.contributor.authorAGUIAR-OLIVEIRA, Manuel H.
dc.contributor.authorMENDONCA, Berenice B.
dc.contributor.authorARNHOLD, Ivo J. P.
dc.identifier.citationHORMONE RESEARCH IN PAEDIATRICS, v.78, n.3, p.165-172, 2012
dc.description.abstractBackground: Mutations in GH-releasing hormone receptor gene (GHRHR) are emerging as the most common cause of autosomal recessive isolated GH deficiency (IGHD). Objective: To search for GHRHR mutations in patients with familial or sporadic IGHD and to investigate founder effects in recurring mutations. Methods: The coding region of GHRHR was entirely amplified and sequenced from DNA of 18 patients with IGHD (16 unrelated) with topic posterior pituitary lobe on MRI. Haplotypes containing promoter SNPs and microsatellites flanking GHRHR were analyzed in patients with c.57+1G>A (IVS1+1G>A) mutation of our previously published kindred and also a Brazilian patient and 2 previously reported Japanese sisters with c. 1146G>A (p.E382E) mutation. Results: A novel homozygous intronic GHRHR c.752-1G>A (IVS7-1G>A) mutation, predicting loss of the constitutive splice acceptor site, was identified in two siblings with IGHD. A compound heterozygous c.[57+1G>A];[1146G>A] and a heterozygous c.527C>T (p.A176V) were found in two sporadic cases. Haplotype analysis provided evidence for a founder effect for the c.57+1G>A mutation and independent recurrence for the c.1146G>A mutation. Conclusion: We report a novel splice-disrupting mutation in GHRHR in 2 siblings and provide evidence that all c.57+1G>A (IVS1+1G>A) mutant chromosomes have the same haplotype ancestor, indicating the occurrence of a founder effect in Brazilian patients with IGHD.
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [99/10692-8, 00/06677-2, 00/14092-4]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [475870/2009-3, 301477/2009-4, 301339/2008-9, 300982/2009-7]
dc.relation.ispartofHormone Research in Paediatrics
dc.subjectGHRHR mutations
dc.subjectIsolated GH deficiency
dc.subjectSplicing mutations
dc.subject.otherghrhr gene
dc.titleGH-Releasing Hormone Receptor Gene: A Novel Splice-Disrupting Mutation and Study of Founder Effects
dc.rights.holderCopyright KARGER
dc.subject.wosEndocrinology & Metabolism
dc.type.categoryoriginal article
dc.type.versionpublishedVersion, Margaret C. S.:Univ Fed Parana, Dept Pediat, BR-80060000 Curitiba, Parana, Brazil, Hiroshi:Univ Tokushima, Tokushima 770, Japan FILHO, Luiz de:Univ Fed Parana, Dept Pediat, BR-80060000 Curitiba, Parana, Brazil, Manuel H.:Univ Fed Sergipe, Dept Med, Aracaju, Brazil
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Appears in Collections:

Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - LIM/25
LIM/25 - Laboratório de Endocrinologia Celular e Molecular

Artigos e Materiais de Revistas Científicas - LIM/42
LIM/42 - Laboratório de Hormônios e Genética Molecular

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