Biologia e Medicina

Abstrato

A BRAT1 Synonymous Mutation Affecting Exon Splicing leads to Lethal Neonatal Rigidity and Multifocal Seizure Syndrome: A Chinese Case Report

Zhihua Luo*, Dengyu Zhou, Min Zhang

Background: Rigidity and Multifocal Seizure Syndrome, Lethal Neonatal (RMFSL, OMIM#614498), is caused by mutations of the BRAT1 gene. Our patient had the typical syndromes of RMFSL, and Trio whole exome sequencing (trio-WES) identified a homozygous synonymous variant (BRAT1:C.1395 (exon10) G>C). Given that the pathogenicity of synonymous mutation (p.Thr465Thr) is most likely underestimated, a further transcriptional study of the father showed that C.1395 (exon10) G>C mutation would result in abnormal splicing, which caused the exon 10 skipping and affected protein features. We first confirmed the pathogenicity of the synonymous mutation of BRAT1 using a transcriptional study.