Identification and Functional Characterization of an ISL1 Mutation Predisposing to Dilated Cardiomyopathy

In this study, the coding regions ofISL1, which encodes a transcription factor critical for embryonic cardiogenesis and postnatal cardiac remodeling, were sequenced in 216 unrelated patients with DCM, and a novel heterozygousISL1 mutation, NM_002202.2: c.631A>T; p.(Lys211*), was identified in a proband. The mutation, which co-segregated with DCM in the family, was absent in 238 unrelated controls, as well as in the Genome Aggregation and the Exome Aggregation Consortium population databases. Functional analyses unveiled that the mutant ISL1 protein lost transcriptional activity alone or in synergy with TBX20 or GATA4, two other transcription factors associated with DCM. These findings indicateISL1 as a new gene of DCM.
Source: Journal of Cardiovascular Translational Research - Category: Cardiology Source Type: research