Identification, clinical manifestation and structural mechanisms of mutations in AMPK associated cardiac glycogen storage disease.

ABSTRACT:

Background

Although 21 causative mutations have been associated with PRKAG2 syndrome, our understanding of the syndrome remains incomplete. The aim of this project is to further investigate its unique genetic background, clinical manifestations, and underlying structural changes.

Methods

We recruited 885 hypertrophic cardiomyopathy (HCM) probands and their families internationally. Targeted next-generation sequencing of sudden cardiac death (SCD) genes was performed. The role of the identified variants was assessed using histological techniques and computational modeling.

Findings

Twelve PRKAG2 syndrome kindreds harboring 5 distinct variants were identified. The clinical penetrance of 25 carriers was 100.0%. Twenty-two family members died of SCD or heart failure (HF).

SUBMITTER: Hu D 

PROVIDER: S-EPMC7132172 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature