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Published on: September 15, 2018
Genetic Spectrum and Cascade Screening of Familial Hypercholesterolemia in Routine Clinical Setting in Hong Kong
Man-Kwan Yip1, Elaine Yin-Wah Kwan2, Jenny Yin-Yan Leung3
1Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong, China.
Insights
Genetic testing identified 25 distinct LDLR variants in Familial Hypercholesterolemia (FH) patients in Asia. Cascade screening proved crucial for early detection of FH cases, improving patient management.
Area of Science:
- Genetics
- Metabolic Disorders
- Cardiovascular Disease
Background:
- Familial Hypercholesterolemia (FH) is a common, underdiagnosed genetic disorder of lipoprotein metabolism.
- Genetic testing for FH has historically been limited in Asia.
- Early diagnosis and management are crucial for preventing cardiovascular complications.
Purpose of the Study:
- To investigate the utility of genetic testing and cascade screening for FH in an Asian population.
- To identify novel LDLR variants associated with FH.
- To evaluate diagnostic performance metrics for FH.
Main Methods:
- Cross-sectional study involving 31 FH probands undergoing genetic testing and 15 individuals undergoing cascade screening.
- Identification and characterization of LDLR variants.
- Comparison of diagnostic performance using treatment intensity, LDL-C levels, and DLCNC scores.
Main Results:
- Identified 25 distinct LDLR variants in 71.0% of unrelated probands.
- Adult probands with confirmed FH often had a family history of premature cardiovascular disease.
- Treatment intensity for LDL-C reduction showed promising diagnostic performance.
- Cascade screening identified individuals with less severe FH phenotypes, highlighting its role in early detection.
Conclusions:
- Genetic testing and cascade screening are vital for accurate FH identification and management in Asia.
- Cascade screening facilitates early detection of undiagnosed FH cases.
- Further research into diagnostic criteria and management strategies for FH is warranted.
Abstract:
Familial hypercholesterolemia (FH) is a prevalent but often underdiagnosed monogenic disorder affecting lipoprotein metabolism, and genetic testing for FH has not been widely conducted in Asia in the past. In this cross-sectional study of 31 probands (19 adults and 12 children) and an addition of 15 individuals (12 adults and 3 children), who underwent genetic testing and cascade screening for FH, respectively, during the period between February 2015 and July 2023, we identified a total of 25 distinct LDLR variants in 71.0% unrelated probands. Among the adult proband cohort, a higher proportion of genetically confirmed cases exhibited a positive family history of premature cardiovascular disease. Treatment intensity required to achieve an approximate 50% reduction in pretreatment low-density lipoprotein cholesterol (LDL-C) exhibited potentially better diagnostic performance compared to pretreatment LDL-C levels, Dutch Lipid Clinic Network Diagnostic Criteria (DLCNC) score, and modified DLCNC score. Adult individuals identified through cascade screening demonstrated less severe phenotypes, and fewer of them met previously proposed local criteria for FH genetic testing compared to the probands, indicating that cascade screening played a crucial role in the early detection of new cases that might otherwise have gone undiagnosed. These findings underscore the significance of genetic testing and cascade screening in the accurate identification and management of FH cases.
