Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/42048
Title: Allelic Variants in Established Hypopituitarism Genes Expand Our Knowledge of the Phenotypic Spectrum
Authors: NAKAGUMA, MarilenaFERREIRA, Nathalia Garcia Bianchi PereiraBENEDETTI, Anna Flavia FigueredoMADI, Mariana CotarelliSILVA, Juliana MoreiraLI, Jun Z.MA, QianyiOZEL, Ayse BilgeFANG, QingNARCIZO, Amanda de MoraesCARDOSO, Lais CavalcaMONTENEGRO, Luciana RibeiroFUNARI, Mariana Ferreira de AssisNISHI, Mirian YumieARNHOLD, Ivo Jorge PradoJORGE, Alexander Augusto de LimaMENDONCA, Berenice Bilharinho deCAMPER, Sally AnnCARVALHO, Luciani R.
Citation: GENES, v.12, n.8, article ID 1128, 12p, 2021
Abstract: We report four allelic variants (three novel) in three genes previously established as causal for hypopituitarism or related disorders. A novel homozygous variant in the growth hormone gene, GH1 c.171delT (p.Phe 57Leufs*43), was found in a male patient with severe isolated growth hormone deficiency (IGHD) born to consanguineous parents. A hemizygous SOX3 allelic variant (p.Met304Ile) was found in a male patient with IGHD and hypoplastic anterior pituitary. YASARA, a tool to evaluate protein stability, suggests that p.Met304Ile destabilizes the SOX3 protein (Delta Delta G = 2.49 kcal/mol). A rare, heterozygous missense variant in the TALE homeobox protein gene, TGIF1 (c.268C>T:p.Arg90Cys) was found in a patient with combined pituitary hormone deficiency (CPHD), diabetes insipidus, and syndromic features of holoprosencephaly (HPE). This variant was previously reported in a patient with severe holoprosencephaly and shown to affect TGIF1 function. A novel heterozygous TGIF1 variant (c.82T>C:p.Ser28Pro) was identified in a patient with CPHD, pituitary aplasia and ectopic posterior lobe. Both TGIF1 variants have an autosomal dominant pattern of inheritance with incomplete penetrance. In conclusion, we have found allelic variants in three genes in hypopituitarism patients. We discuss these variants and associated patient phenotypes in relation to previously reported variants in these genes, expanding our knowledge of the phenotypic spectrum in patient populations.
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Artigos e Materiais de Revistas Científicas - FM/MCM
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ODS/03 - Saúde e bem-estar


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