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

ABSTRACT 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; NM₀05751. 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.