Craniofrontonasal Syndrome Caused by Introduction of a Novel UATG in the 5'UTR of

Overview

Journal Mol Syndromol

Date 2019 Apr 13

PMID 30976278

Citations 8

Authors

Vanessa L Romanelli Tavares

Erika Kague

Camila M Musso

Thiago G P Alegria

Renato S Freitas

Debora R Bertola

Stephen R F Twigg

Maria R Passos-Bueno

Affiliations

Soon will be listed here.

Abstract

Craniofrontonasal syndrome (CFNS) is an X-linked disorder caused by 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 , 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 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 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 .

Citing Articles

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