Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders

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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.authorTUSSET, Cintia
dc.contributor.authorNOEL, Sekoni D.
dc.contributor.authorTRARBACH, Ericka B.
dc.contributor.authorSILVEIRA, Leticia F. G.
dc.contributor.authorJORGE, Alexander A. L.
dc.contributor.authorBRITO, Vinicius N.
dc.contributor.authorCUKIER, Priscila
dc.contributor.authorSEMINARA, Stephanie B.
dc.contributor.authorMENDONCA, Berenice B. de
dc.contributor.authorKAISER, Ursula B.
dc.contributor.authorLATRONICO, Ana Claudia
dc.date.accessioned2013-07-30T14:41:57Z
dc.date.available2013-07-30T14:41:57Z
dc.date.issued2012
dc.description.abstractObjective: To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders. Subjects and methods: Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH), and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced. Results: We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C > T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L, and p.W275* variants were identified in three unrelated males with normosmic IHH. Conclusion: Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype.
dc.description.abstractOBJETIVO: Investigar a presença de variantes nos genes TAC3 e TACR3, os quais codificam a NKB e seu receptor (NK3R), respectivamente, em uma coorte de pacientes com distúrbios puberais centrais idiopáticos. SUJEITOS E MÉTODOS: Duzentos e trinta e sete pacientes foram estudados: 114 com puberdade precoce central (PPC), 73 com hipogonadismo hipogonadotrófico isolado normósmico (HHI) e 50 com retardo constitucional do crescimento e desenvolvimento (RCCD). O grupo controle consistiu de 150 indivíduos brasileiros que apresentaram desenvolvimento puberal normal. O DNA genômico foi extraído de sangue periférico, e as regiões codificadoras dos genes TAC3 e TACR3 foram amplificadas e sequenciadas automaticamente. RESULTADOS: Uma variante (p.A63P) foi identificada na NKB, e quatro variantes, p.G18D, p.L58L (c.172C>T), p.W275X e p.A449S, foram identificadas no NK3R, as quais foram ausentes no grupo controle. A variante p.A63P foi identificada em uma menina com PPC, e a variante p.A449S, em uma menina com RCCD. As variantes previamente descritas, p.G18D, p.L58L e p.W275X, foram identificadas em três indivíduos com HHI normósmico do sexo masculino não relacionados. CONCLUSÃO: Variantes raras nos genes TAC3 e TACR3 foram identificadas em pacientes com distúrbios puberais centrais idiopáticos. Mutações de perda de função no gene TACR3 foram associadas com o fenótipo de HHI normósmico.
dc.description.indexMEDLINE
dc.description.sponsorshipFapesp [05/04726-0]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [302825/2011-8, 305743/2011-8]
dc.description.sponsorshipEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH) [U54 HD28138]
dc.identifier.citationARQUIVOS BRASILEIROS DE ENDOCRINOLOGIA E METABOLOGIA, v.56, n.9, p.646-652, 2012
dc.identifier.doi10.1590/s0004-27302012000900008
dc.identifier.issn0004-2730
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/503
dc.language.isoeng
dc.publisherSBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA
dc.relation.ispartofArquivos Brasileiros de Endocrinologia e Metabologia
dc.rightsopenAccess
dc.rights.holderCopyright SBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA
dc.subjectneurokinin B receptor
dc.subjectcentral precocious puberty
dc.subjectnormosmic isolated hypogonadotropic hypogonadism
dc.subjectconstitutional delay of growth and puberty
dc.subjectNeurocinina B
dc.subjectreceptor da neurocinina B
dc.subjectpuberdade precoce central
dc.subjecthipogonadismo hipogonadotrófico isolado normósmico
dc.subjectretardo constitucional do crescimento e desenvolvimento
dc.subject.othergonadotropin-releasing-hormone
dc.subject.otherhypogonadotropic hypogonadism
dc.subject.otherneurokinin-b
dc.subject.othertachykinin receptors
dc.subject.otherconstitutional delay
dc.subject.otherpropeptide mutation
dc.subject.otherarcuate nucleus
dc.subject.otherreproduction
dc.subject.otherinheritance
dc.subject.otherpatterns
dc.subject.wosEndocrinology & Metabolism
dc.titleMutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders
dc.title.alternativeAnálise de mutações nos genes TAC3 e TACR3 em pacientes com distúrbios puberais centrais idiopáticos
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalNOEL, Sekoni D.:Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA; Brigham & Womens Hosp, Harvard Ctr Reprod Sci, Boston, MA 02115 USA
hcfmusp.author.externalSEMINARA, Stephanie B.:Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA; Massachusetts Gen Hosp, Harvard Ctr Reprod Sci, Boston, MA 02114 USA
hcfmusp.author.externalKAISER, Ursula B.:Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA; Brigham & Womens Hosp, Harvard Ctr Reprod Sci, Boston, MA 02115 USA
hcfmusp.citation.scopus42
hcfmusp.contributor.author-fmusphcCINTIA TUSSET
hcfmusp.contributor.author-fmusphcERICKA BARBOSA TRARBACH
hcfmusp.contributor.author-fmusphcLETICIA FERREIRA GONTIJO SILVEIRA
hcfmusp.contributor.author-fmusphcALEXANDER AUGUSTO DE LIMA JORGE
hcfmusp.contributor.author-fmusphcVINICIUS NAHIME DE BRITO
hcfmusp.contributor.author-fmusphcPRISCILLA CUKIER
hcfmusp.contributor.author-fmusphcBERENICE BILHARINHO DE MENDONCA
hcfmusp.contributor.author-fmusphcANA CLAUDIA LATRONICO XAVIER
hcfmusp.description.beginpage646
hcfmusp.description.endpage652
hcfmusp.description.issue9
hcfmusp.description.volume56
hcfmusp.lim.ref2012
hcfmusp.origemWOS
hcfmusp.origem.pubmed23329188
hcfmusp.origem.scieloSCIELO:S0004-27302012000900008
hcfmusp.origem.scopus2-s2.0-84872796582
hcfmusp.origem.wosWOS:000313706900008
hcfmusp.publisher.cityRIO DE JANEIRO, RJ
hcfmusp.publisher.countryBRAZIL
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hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
hcfmusp.remissive.sponsorshipNIH
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