A recurrent de novo splice site variant involving DNM1 exon 10a causes developmental and epileptic encephalopathy through a dominant-negative mechanism

Heterozygous pathogenic variants in DNM1 cause developmental and epileptic encephalopathy. Here, we perform RNA sequencing in brain samples and find non-canonical, alternatively spliced transcripts are the most abundant. We highlight the importance of considering relevant isoforms for variant interpretation and the possibility of intronic variants causing disease through dominant-negative mechanisms.

Source: The American Journal of Human Genetics - November 21, 2022 Category: Genetics & Stem Cells Authors: Shridhar Parthasarathy, Sarah McKeown Ruggiero, Antoinette Gelot, Fernanda C Soardi, Beth ânia F R Ribeiro, Douglas E V Pires, David B Ascher, Alain Schmitt, Caroline Rambaud, Alfonso Represa, Hongbo M Xie, Laina Lusk, Olivia Wilmarth, Pamela Pojomovsky Tags: Article Source Type: research