Identification and characterization of novel low-density lipoprotein receptor mutations of familial hypercholesterolaemia patients in Taiwan

Background Familial hypercholesterolaemia (FH) is an autosomal dominant disease associated with a very high risk of coronary vascular disease. The study objective was to identify patients with FH in Taiwan and characterize novel mutations. Materials and methods Fifty-one patients with suspected FH living in Taiwan were screened for mutations in both the low-density lipoprotein (LDL) receptor and the apolipoprotein (apoB) genes using the multiplex polymerase chain reaction and exon-by-exon DNA sequencing technique. Functional consequences on LDL receptor activity were characterized in vitro for novel mutations and family pedigree was also analyzed. Results Thirteen different functional mutations in the LDL receptor gene and one mutation in the apoB gene were found in 21 patients. Among the 13 mutations in the LDL receptor gene, 10 were single-point missense mutations, one was a two-point mutation in the same allele, one was a non-sense mutation and one was a frame-shift mutation. There were three novel mutations, including two missense mutations (M510K and W512R) and one frame-shift mutation (1953 delTA mutation). The characterization of missense M510K retained 36.2% of the activity of the normal receptor. Conversely, frame-shift 1953 delTA and missense W512R led to defective proteins, with only 0-6% of normal receptor activity. Conclusions The study identified 13 LDL receptor gene mutations and characterized three novel mutations causing FH in Taiwan. This facilitated a better understanding of FH among the Chinese population and may enable diagnosis of FH at the molecular level at a presymptomatic, early age.