Allelic Variants in Established Hypopituitarism Genes Expand Our Knowledge of the Phenotypic Spectrum.

Autor:	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.; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil., Madi MC; 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., 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; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA., 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; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil., Cardoso LC; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil., Montenegro 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.; 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.; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil., Nishi MY; 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.; 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; Genetic Endocrinology Unit (LIM25), Division of Endocrinology, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP), 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.; Laboratorio de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil., Camper SA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA., 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.
Jazyk:	angličtina
Zdroj:	Genes [Genes (Basel)] 2021 Jul 25; Vol. 12 (8). Date of Electronic Publication: 2021 Jul 25.
DOI:	10.3390/genes12081128
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu