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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 8
[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
Total Affiliations: 7
Document type: Journal article
Source: MOLECULAR SYNDROMOLOGY; v. 10, n. 1-2, p. 40-47, 2019.
Web of Science Citations: 1

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)

FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC