Familial hypercholesterolaemia: detection, diagnosis and phenotype-genotype correlations

Khemanganee Eishwarya Liyanage

    Research output: ThesisDoctoral Thesis

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    [Truncated abstract] The work presented in this thesis on Familial Hypercholesterolaemia (FH) has been divided into chapters based on more focused areas relating to FH. A critical review of the current literature serves as an introduction, followed by a general methods section. The research on Familial Ligand-Defective Apolipoprotein B-100 (FDB) is presented next as a separate chapter, detailing the development and testing of a novel method for the detection of FDB. The fourth chapter presents two cases of homozygous FH in Western Australia, discovered during the course of screening patients recruited through the Royal Perth Hospital lipid disorders clinic. This fifth chapter discusses the technical challenges associated with the principles and methods for screening for FH and the sixth chapter presents the results of a comprehensive screen of coronary heart disease (CHD) patients for FH-causing mutations. A general concluding chapter summarises the work presented and completes the thesis. FH is an autosomal co-dominant disorder of lipid metabolism, most commonly resulting from mutations in the low density lipoprotein receptor (LDLR) gene, which affects 1 in 500 individuals in the heterozygous form. Worldwide, the incidence of FH varies, with certain populations demonstrating greater incidences of FH due to founder effects. FH can be recognised by the hallmark features such as xanthomata and arcus cornea, which result from cholesterol deposits in the tendons and cornea respectively. The manifestation of these features is more pronounced in homozygotes in comparison to heterozygous patients who still possess one normal allele. These features form part of all of the three different existing paradigms for the diagnosis of FH, along with other considerations such as plasma low density lipoprotein-cholesterol (LDL-C) levels, family history of heart disease and the detection of disease-causing mutations in the LDLR and other associated genes, including the LDLR
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2009


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