Whole exome sequencing identifies concurrent

Background: Sitosterolemia and Familial hypercholesterolemia (FH) represent two genetically distinct lipid metabolism disorders marked by disparate inheritance mechanisms and therapeutic responses. It is typically inherited in an autosomal dominant pattern due to mutations in the Objective: In this paper, we report what is likely the first genetically confirmed case of compound heterozygosity involving both sitosterolemia and familial hypercholesterolemia in a Saudi Arabian consanguineous family. This unique case highlights the complex diagnostic challenges and therapeutic considerations in managing overlapping dyslipidemia phenotypes. Methods: A multigenerational family was recruited from the Diabetes and Endocrinology Center in Jazan, Saudi Arabia. Comprehensive clinical evaluations were conducted, including family history, physical examination, and lipid profiling. Whole exome sequencing (WES) was performed using the CentoXome Findings: WES revealed a novel heterozygous frameshift deletion in Conclusion: This study presents the first extensive molecular characterization of a dual FH-sitosterolemia phenotype. It emphasizes the critical role of genomic diagnostics in managing complex lipid disorders and supports personalized medicine approaches, especially in consanguineous populations where blended phenotypes may be underrecognized.