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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.)

Craniofrontonasal Syndrome Caused by Introduction of a Novel uATG in the 5 ` UTR of EFNB1

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Autor(es):
Romanelli Tavares, Vanessa L. [1, 2] ; Kague, Erika [1, 2, 3] ; Musso, Camila M. [1, 2] ; Alegria, Thiago G. P. [2] ; Freitas, Renato S. [4, 5] ; Bertola, Debora R. [1, 2, 6] ; Twigg, Stephen R. F. [7] ; Passos-Bueno, Maria R. [1, 2]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ctr Pesquisa Genoma Humano & Celulas Tronco CEGH, Fac Med, Hosp Clin, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Genet & Biol Evolut, Inst Biociencias, Hosp Clin, Fac Med, Sao Paulo - Brazil
[3] Univ Bristol, Dept Physiol Pharmacol & Neurosci, Bristol, Avon - England
[4] Univ Fed Parana, Curitiba, Parana - Brazil
[5] Ctr Atendimento Integral Fissurado Labio Palatal, Curitiba, Parana - Brazil
[6] Univ Sao Paulo, Hosp Clin, Inst Crianca, Fac Med, Sao Paulo - Brazil
[7] Univ Oxford, MRC Weatherall Inst Mol Med, Clin Genet Grp, Oxford - England
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: MOLECULAR SYNDROMOLOGY; v. 10, n. 1-2, p. 40-47, 2019.
Citações Web of Science: 1
Resumo

Craniofrontonasal syndrome (CFNS) is an X-linked disorder caused by EFNB1 mutations in which females are more severely affected than males. Severe male phenotypes are associated with mosaicism, supporting cellular interference for sex bias in this disease. Although many variants have been found in the coding region of EFNB1, only 2 pathogenic variants have been identified in the same nucleotide in 5' UTR, disrupting the stop codon of an upstream open reading frame (uORF). uORFs are known to be part of a wide range of post-transcriptional regulation processes, and just recently, their association with human diseases has come to light. In the present study, we analyzed EFNB1 in a female patient with typical features of CFNS. We identified a variant, located at c.-411, creating a new upstream ATG (uATG) in the 5'UTR of EFNB1, which is predicted to alter an existing uORF. Dual-luciferase reporter assays showed significant reduction in protein translation, but no difference in the mRNA levels. Our study demonstrates, for the first time, the regulatory impact of uATG formation on EFNB1 levels and suggests that this should be the target region in molecular diagnosis of CFNS cases without pathogenic variants in the coding and splice sites regions of EFNB1. (c) 2018 S. Karger AG, Basel (AU)

Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
Beneficiário:Mayana Zatz
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs