Cosegregation of a novel mutation in the sixth transmembrane segment of the luteinizing/choriogonadotropin hormone receptor with two Brazilian siblings with severe testotoxicosis

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dc.citation.issue2
dc.citation.volume42
dc.contributor.authorSiviero-Miachon, Adriana Aparecida [UNIFESP]
dc.contributor.authorKizys, Marina Malta Letro [UNIFESP]
dc.contributor.authorRibeiro, Manuela M. [UNIFESP]
dc.contributor.authorGarcia, Fabiola Esgrignoli [UNIFESP]
dc.contributor.authorSpinola-Castro, Angela Maria [UNIFESP]
dc.contributor.authorSilva, Magnus Regios Dias da Silva [UNIFESP]
dc.coveragePhiladelphia
dc.date.accessioned2020-07-31T12:46:42Z
dc.date.available2020-07-31T12:46:42Z
dc.date.issued2017
dc.description.abstractPurpose: Testotoxicosis is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor (LHCGR) gene. The aim of this study was to describe two Brazilian siblings with testotoxicosis, to confirm the molecular diagnosis, and to perform an in silico analysis of a novel mutation in the hot spot of the LHCGR gene. Materials and methods: Molecular analysis of the mutation on the LHCGR gene was performed by direct Sanger sequencing, followed by an in silico analysis using HOPE bioinformatics tool to predict a functional defect of the mutant. Results: Both patients presented with gonadotropin-independent precocious puberty before the age of four years. Genetic analysis revealed a novel non-maternally inherited p.Asp578Val mutation of the LHCGR gene. An in silico analysis showed that the p.Asp578Val mutation disturbed amino acid physicochemical features regarding its size, charge, and hydrophobicity value. Conclusions: Clinical and hormonal profile of the siblings here evaluated was not different while compared to those patients previously described. An in silico mutation analysis reinforced the causative role of recurrent activating mutations in the intracellular loop and transmembrane helices of the LHCGR. The segregation of this mutation with the offsprings' phenotype indicated that it is causative.en
dc.description.affiliationFed Univ Sao Paulo UNIFESP EPM, Dept Pediat, Div Pediat Endocrinol, 442 Borges Lagoa St, BR-04023062 Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Med, Lab Mol & Translat Endocrinol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo (UNIFESP) EPM, Dept Pediat, Div Pediat Endocrinol, 442 Borges Lagoa St, BR-04023062 Sao Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo (UNIFESP), Dept Med, Lab Mol & Translat Endocrinol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: 2006/60402-1
dc.description.sponsorshipIDFAPESP: 2011/20747-8
dc.description.sponsorshipIDFAPESP: 2012/01628-0
dc.description.sponsorshipIDFAPESP: 2014/15948-2
dc.format.extent117-124
dc.identifierhttp://dx.doi.org/10.1080/07435800.2016.1217005
dc.identifier.citationEndocrine Research. Philadelphia, v. 42, n. 2, p. 117-124, 2017.
dc.identifier.doi10.1080/07435800.2016.1217005
dc.identifier.issn0743-5800
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56317
dc.identifier.wosWOS:000399655700006
dc.language.isoeng
dc.publisherTaylor & Francis Inc
dc.relation.ispartofEndocrine Research
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectIn silico analysisen
dc.subjectluteinizing hormoneen
dc.subjectpubertyen
dc.subjectprecociousen
dc.subjectreceptorsen
dc.subjectLHen
dc.titleCosegregation of a novel mutation in the sixth transmembrane segment of the luteinizing/choriogonadotropin hormone receptor with two Brazilian siblings with severe testotoxicosisen
dc.typeinfo:eu-repo/semantics/article
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