Genetic Landscape of Familial Hypercholesterolemia in Southern India: Novel Mutations and Clinical Implications

Familial hypercholesterolemia (FH) is a prevalent autosomal dominant disorder characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) levels, predisposing individuals to premature cardiovascular disease (CVD). This study aimed to elucidate the genetic underpinnings of FH in patients residing in Telangana State, India, by identifying pathogenic variants associated with the disease. We employed a comprehensive approach, initially identifying probands with suspected FH using the established Dutch Lipid Clinic Network (DLCN) score, followed by a cascade screening of their first-degree relatives. Targeted exome sequencing, coupled with detailed pedigree analysis, was subsequently performed to pinpoint FH-associated genetic variants. Our investigation revealed a spectrum of genetic alterations, encompassing both previously documented and novel high-impact mutations within genes critically involved in FH pathogenesis.