• U K Ibe, R Whittall, S E Humphries, G Pilcher, and F Raal.
• Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Institute of Cardiovascular Sciences, University College London, UK. ken.ibe.11@ucl.ac.uk.
• S. Afr. Med. J. 2017 Jan 30; 107 (2): 145-148.

BackgroundFamilial hypercholesterolaemia (FH) is usually caused by mutations in three genes (LDLR, APOB and PCSK9).ObjectiveTo identify the spectrum of FH-causing mutations in black South African (SA) patients.MethodsDNA samples of 16 unrelated South African FH patients with elevated low-density lipoprotein cholesterol levels, tendon xanthomas and corneal arcus (3 clinically homozygous FH and 13 heterozygous FH) of ethnic African origin were screened for mutations in the LDLR (coding region, promoter and intron/exon boundaries), APOB (part of exon 26) and PCSK9 genes (exon 7), using high-resolution melting.ResultsEight LDLR mutations were identified, for an overall detection rate of 8/19 predicted FH-causing alleles (42.1%). The previously reported six base pair deletion p.(D47_G48del) was found in two patients, and two novel variants (c.1187-25T>C and c.1664T>G p.(L555R)) were found, both predicted to be pathogenic using in silico web-based predictive algorithms. No pathogenic variants in APOB or PCSK9 were found.ConclusionsThese findings contribute to the knowledge of allelic heterogeneity in the spectrum of FH-causing mutations in black SA patients, signifying their ancestral diversity. The relatively low overall detection rate may reflect locus heterogeneity of the FH phenotype in black SA FH patients.

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