Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review.
The clinical phenotype of heterozygous familial hypercholesterolemia (FH) is characterized by increased plasma levels of total cholesterol and low density lipoprotein cholesterol, tendinous xanthomata, and premature symptoms of coronary heart disease. It is inherited as an autosomal dominant disorder with homozygotes having a more severe phenotype than do heterozygotes. FH can result from mutations in the low density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), and the recently identified proprotein convertase subtilisin/kexin type 9 gene (PCSK9). To date, over 700 variants have been identified in the LDLR gene. With the exception of a small number of founder populations where one or two mutations predominate, most geographically based surveys of FH subjects show a large number of mutations segregating in a given population. Studies of the prevalence of FH would be improved by the use of a consistent and uniformly applied clinical definition. Because FH responds well to drug treatment, early diagnosis to reduce atherosclerosis risk is beneficial. Cascade testing of FH family members is cost effective and merits further research. For screening to be successful, public health and general practitioners need to be aware of the signs and diagnosis of FH and the benefits of early treatment.
Institute for Public Health Genetics and Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, 1959 NE Pacific Avenue, Seattle, WA 98195, USA. maustin@u.washington.edu
Melissa A
MA
Austin
Carolyn M
CM
Hutter
Ron L
RL
Zimmern
Steve E
SE
Humphries
D000328:Adult; D005260:Female; D005828:Genetics, Population / Q000706:statistics & numerical data*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015995:Prevalence; D011973:Receptors, LDL / Q000235:genetics*
D011973:Receptors, LDL