A Novel A-Kinase-Anchoring Protein 9 Variant in Premature Coronary Artery Disease: A Case Series.

BACKGROUND

Familial premature coronary artery disease (CAD) is often associated with genetic variants. This study investigated potential causal variants in a Chinese pedigree with premature CAD.

METHODS

In total, nine family members were included in the study (six CAD patients and three unaffected controls). Whole-exome sequencing (WES) was performed on six family members (including four patients and two unaffected controls), and the candidate variant was further validated by Sanger sequencing in four individuals.

RESULTS

A strong linkage between c.6406C>G (p.Gln2136Glu; NM_005751.5) in AKAP9 (A-KINASE ANCHOR PROTEIN 9; OMIM 604001) and premature CAD was detected in the pedigree. Functional analysis revealed that the c.6406C>G variant in AKAP9 decreased the interaction between AKAP9 and PRKAR2A. This association was first detected in premature CAD patients.

CONCLUSIONS

Our findings indicate that c.6406C>G in the AKAP9 gene could be a causal variant for premature CAD in the Chinese population.