Your browser doesn't support javascript.
loading
Allelic Variants in Established Hypopituitarism Genes Expand Our Knowledge of the Phenotypic Spectrum.
Nakaguma, Marilena; Ferreira, Nathalia Garcia Bianchi Pereira; Benedetti, Anna Flavia Figueredo; Madi, Mariana Cotarelli; Silva, Juliana Moreira; Li, Jun Z; Ma, Qianyi; Bilge Ozel, Ayse; Fang, Qing; Narcizo, Amanda de Moraes; Cardoso, Laís Cavalca; Montenegro, Luciana Ribeiro; Funari, Mariana Ferreira de Assis; Nishi, Mirian Yumie; Arnhold, Ivo Jorge Prado; Jorge, Alexander Augusto de Lima; Mendonca, Berenice Bilharinho de; Camper, Sally Ann; Carvalho, Luciani R.
Afiliação
  • Nakaguma M; Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM/42, Division of Endocrinology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Av Dr Eneas de Carvalho Aguiar, 155, 2 Andar, Bloco 6, São Paulo 05403-000, Brazil.
  • Ferreira NGBP; Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM/42, Division of Endocrinology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Av Dr Eneas de Carvalho Aguiar, 155, 2 Andar, Bloco 6, São Paulo 05403-000, Brazil.
  • Benedetti AFF; Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM/42, Division of Endocrinology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Av Dr Eneas de Carvalho Aguiar, 155, 2 Andar, Bloco 6, São Paulo 05403-000, Brazil.
  • Madi MC; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil.
  • Silva JM; Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM/42, Division of Endocrinology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Av Dr Eneas de Carvalho Aguiar, 155, 2 Andar, Bloco 6, São Paulo 05403-000, Brazil.
  • Li JZ; Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM/42, Division of Endocrinology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Av Dr Eneas de Carvalho Aguiar, 155, 2 Andar, Bloco 6, São Paulo 05403-000, Brazil.
  • Ma Q; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA.
  • Bilge Ozel A; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA.
  • Fang Q; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA.
  • Narcizo AM; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA.
  • Cardoso LC; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil.
  • Montenegro LR; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil.
  • Funari MFA; Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM/42, Division of Endocrinology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Av Dr Eneas de Carvalho Aguiar, 155, 2 Andar, Bloco 6, São Paulo 05403-000, Brazil.
  • Nishi MY; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil.
  • Arnhold IJP; Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM/42, Division of Endocrinology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Av Dr Eneas de Carvalho Aguiar, 155, 2 Andar, Bloco 6, São Paulo 05403-000, Brazil.
  • Jorge AAL; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil.
  • Mendonca BB; Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM/42, Division of Endocrinology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Av Dr Eneas de Carvalho Aguiar, 155, 2 Andar, Bloco 6, São Paulo 05403-000, Brazil.
  • Camper SA; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil.
  • Carvalho LR; Developmental Endocrinology Unit, Laboratory of Hormones and Molecular Genetics LIM/42, Division of Endocrinology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Av Dr Eneas de Carvalho Aguiar, 155, 2 Andar, Bloco 6, São Paulo 05403-000, Brazil.
Genes (Basel) ; 12(8)2021 07 25.
Article em En | MEDLINE | ID: mdl-34440302
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 (ΔΔG = 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.
Assuntos
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Proteínas Repressoras / Proteínas de Homeodomínio / Hormônio do Crescimento Humano / Alelos / Fatores de Transcrição SOXB1 / Hipopituitarismo Tipo de estudo: Prognostic_studies Limite: Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Genes (Basel) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Proteínas Repressoras / Proteínas de Homeodomínio / Hormônio do Crescimento Humano / Alelos / Fatores de Transcrição SOXB1 / Hipopituitarismo Tipo de estudo: Prognostic_studies Limite: Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Genes (Basel) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça