Discovery of PPP2R3A and TMX3 pathogenic variants in a Zhuang family with coronary artery disease using whole-exome sequencing.

Whole-exome sequencing (WES) was used to explore pathogenic variants present in a Zhuang family with coronary artery disease (CAD). The 11 Zhuang family members enrolled in this study include three generations of direct relatives with a history of CAD. All members currently live in Guangxi Zhuang Autonomous Region (China), in which all members were also born. Clinical and biochemical tests were performed on the members who were divided into the CAD group (four members), the high-risk CAD group (four members), or normal control group (three members). Whole-exome sequencing was performed on two randomly selected CAD members and one control member in order to screen for candidate genes. All members of the family were genetically verified using Sanger sequencing. Bioinformatics analysis performed on WES data led to the discovery of five candidate genes. Having been confirmed using Sanger sequencing, two pathogenic mutations, PPP2R3A (c.721G; p.Glu241Lys>A) and TMX3 (c.1035 + 38delA), were found in four members of the CAD group and two members of the high-risk group. These variants were not detected in the three control group members. PPP2R3A and TMX3 may be new pathogenic mutations associated with CAD in the Zhuang population of Guangxi province.