SOS1 Gain-of-Function Variants in Dilated Cardiomyopathy.

ABSTRACT:

Background

Dilated cardiomyopathy (DCM) is a genetically heterogeneous cardiac disease characterized by progressive ventricular enlargement and reduced systolic function. Here, we report genetic and functional analyses implicating the rat sarcoma signaling protein, SOS1 (Son of sevenless homolog 1), in DCM pathogenesis.

Methods

Exome sequencing was performed on 412 probands and family members from our DCM cohort, identifying several SOS1 variants with potential disease involvement. As several lines of evidence have implicated dysregulated rat sarcoma signaling in the pathogenesis of DCM, we assessed functional impact of each variant on the activation of ERK (extracellular signal-regulated kinase), AKT (protein kinase B), and JNK (c-Jun N-terminal kinase) pathways. Rel

SUBMITTER: Cowan JR 

PROVIDER: S-EPMC7462086 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature