Study on Gene Mutations of Hereditary Heart Diseases in Cases of Yunnan Sudden Unexplained Death

Background Yunnan sudden unexplained death (YNSUD) is a regional public health issue with unclear etiology, characterized by temporal, geographical, and familial clustering. This study aimed to identify pathogenic genetic mutations in hereditary heart disease among YNSUD cases and explore their etiological association. Methods Whole-exome sequencing was performed on 11 YNSUD cases and 11 healthy controls. Mutations were validated by Sanger sequencing, and functional predictions were conducted using SIFT, PolyPhen2, and Mutation Taster. Family history was investigated for genetic analysis. Results Eighty-one point eight percent (9/11) of YNSUD cases carried 39 unique mutations in 14 genes associated with hereditary heart disease, including TTN, DMD, and DSP. Eighty-two point two percent (32/39) of mutations were predicted to be pathogenic. Eight cases (72.7%) had compound mutations (2–16 mutations per case). A novel mutation (DMD:exon49:c.C7151A:p.S2384Y) was identified. Family clustering was observed, e.g., mother-daughter pair LM and LXL shared TTN mutations. No overlapping mutations were found between cases and controls. Conclusions YNSUD is closely associated with pathogenic mutations in hereditary heart disease genes, highlighting the need for genetic screening in high-risk populations to reduce sudden death risk.