Haploinsufficiency of KMT2B, Encoding the Lysine-Specific Histone Methyltransferase 2B, Results in Early-Onset Generalized Dystonia.

ABSTRACT: Early-onset generalized dystonia represents the severest form of dystonia, a hyperkinetic movement disorder defined by involuntary twisting postures. Although frequently transmitted as a single-gene trait, the molecular basis of dystonia remains largely obscure. By whole-exome sequencing a parent-offspring trio in an Austrian kindred affected by non-familial early-onset generalized dystonia, we identified a dominant de novo frameshift mutation, c.6406delC (p.Leu2136Serfs^∗17), in KMT2B, encoding a lysine-specific methyltransferase involved in transcriptional regulation via post-translational modification of histones. Whole-exome-sequencing-based exploration of a further 30 German-Austrian individuals with early-onset generalized dystonia uncovered another three deleterious mutati

SUBMITTER: Zech M 

PROVIDER: S-EPMC5142117 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature