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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

A study of splicing mutations in disorders of sex development

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Autor(es):
de Calais, Flavia Leme [1, 2] ; Smith, Lindsay D. [2, 3] ; Raponi, Michela [2] ; Maciel-Guerra, Andrea Trevas [4] ; Guerra-Junior, Gil [5] ; de Mello, Maricilda Palandi [1] ; Baralle, Diana [2, 6]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, Ctr Biol Mol & Engn Genet, Campinas, SP - Brazil
[2] Univ Southampton, Fac Med, Human Dev & Hlth, Southampton, Hants - England
[3] Univ Southampton, Fac Med, Canc Sci Unit, Southampton, Hants - England
[4] Univ Estadual Campinas, Dept Genet, Fac Ciencias Med, Campinas, SP - Brazil
[5] Univ Estadual Campinas, Dept Pediat, Fac Ciencias Med, Campinas, SP - Brazil
[6] Southampton Univ Hosp NHS Trust, Wessex Clin Genet Serv, Southampton, Hants - England
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 7, NOV 24 2017.
Citações Web of Science: 1
Resumo

The presence of splicing sequence variants in genes responsible for sex development in humans may compromise correct biosynthesis of proteins involved in the normal development of gonads and external genitalia. In a cohort of Brazilian patients, we identified mutations in HSD17B3 and SRD5A2 which are both required for human sexual differentiation. A number of these mutations occurred within regions potentially critical for splicing regulation. Minigenes were used to validate the functional effect of mutations in both genes. We evaluated the c. 277 + 2 T > G mutation in HSD17B3, and the c. 544 G > A, c. 548-44 T > G and c. 278delG mutations in SRD5A2. We demonstrated that these mutations altered the splicing pattern of these genes. In a genomic era these results illustrate, and remind us, that sequence variants within exon-intron boundaries, which are primarily identified for diagnostic purposes and have unknown pathogenicity, need to be assessed with regards to their impact not only on protein expression, but also on mRNA splicing. (AU)

Processo FAPESP: 11/24119-1 - Diagnóstico Molecular da Deficiência de 5±-Redutase Tipo II em Irmãos 46,XY de uma Família Brasileira com Distúrbio do Desenvolvimento Sexual
Beneficiário:Maricilda Palandi de Mello
Modalidade de apoio: Auxílio à Pesquisa - Publicações científicas - Artigo