Haplotype associations of three DNA polymorphisms at the human low density lipoprotein receptor gene locus in familial hypercholesterolaemia.

Kotze, Maritha J.; Langenhoven, E.; Retief, A.E.; Steyn, Krisela; Marais, M. P.; Grobbelaar, Johanna J.; Oosthuizen, C. J. J.; Weich, Hellmuth; Benadé, A. J. S.

doi:10.1136/jmg.24.12.750

Cited by 29 publications

(18 citation statements)

References 8 publications

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“…Ninety six people drawn from the same population (19 Pedis, 21 Sothos, 27 Xhosas, and 29 Zulus) were sampled as controls. TC, high density lipoprotein cholesterol (HDLC), and triglyceride (TG) determinations and extraction of genomic DNA were performed using standard methods 13. Plasma LDL cholesterol (LDLC) concentrations were calculated with the Friedewald formula (LDLC=TC−(HDL+TG/2.18)) 14…”

Section: Methodsmentioning

confidence: 99%

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia

Thiart

Scholtz

Vergotine

et al. 2000

Journal of Medical Genetics

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In South Africa, the high prevalence of familial hypercholesterolaemia (FH) among Afrikaners, Jews, and Indians as a result of founder genes is in striking contrast to its reported virtual absence in the black population in general. In this study, the molecular basis of primary hypercholesterolaemia was studied in 16 Africans diagnosed with FH. DNA analysis using three screening methods resulted in the identification of seven diVerent mutations in the coding region of the low density lipoprotein (LDLR) gene in 10 of the patients analysed. These included a 6 bp deletion (GCGATG) accounting for 28% of defective alleles, and six point mutations (D151H, R232W, R385Q, E387K, P678L, and R793Q) detected in single families. The Sotho patient with missense mutation R232W was also heterozygous for a de novo splicing defect 313+1G→A. Several silent mutations/ polymorphisms were detected in the LDLR and apolipoprotein B genes, including a base change (g→t) at nucleotide position −175 in the FP2 LDLR regulatory element. This promoter variant was detected at a significantly higher (p<0.05) frequency in FH patients compared to controls and occurred in cis with mutation E387K in one family. Analysis of four intragenic LDLR gene polymorphisms showed that the same chromosomal background was identified at this locus in the four FH patients with the 6 bp deletion. Detection of the 6 bp deletion in Xhosa, Pedi, and Tswana FH patients suggests that it is an ancient mutation predating tribal separation approximately 3000 years ago.

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Section: Methodsmentioning

confidence: 99%

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia

Thiart

Scholtz

Vergotine

et al. 2000

Journal of Medical Genetics

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“…Methods used in determination of plasma lipid levels and preparation of DNA have been described elsewhere (Kotze et al, 1987). The 3'-half of exon 4 of the LDLR gene was amplified using the polymerase chain reaction (PCR) according to Kotze et al (1991).…”

Section: Methodsmentioning

confidence: 99%

A de novo duplication in the low density lipoprotein receptor gene

et al. 1995

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“…The Cypriot population is mostly of Greek descent and has had significant contacts with many other Caucasian populations. Plasma lipid determinations and genomic DNA extractions were performed as previously described (Kotze et al 1987). Genomic DNA of the index patient was screened for the disease-causing mutation by combined heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis according to Kotze et al (1995).…”

Section: Methodsmentioning

confidence: 99%

A double mutant LDL receptor allele in a Cypriot family with heterozygous familial hypercholesterolemia

et al. 1997

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Two novel mutations Q363X and D365E were identified in the low-density lipoprotein receptor gene in a Cypriot patient with heterozygous familial hypercholesterolemia. Restriction enzyme analysis of the index case and seven of her family members, by using AvaII and PvuII respectively, demonstrated that the two exon 8 mutations are transmitted in cis within the family. The disease phenotype is probably caused by the stop-363 mutation; this would result in a truncated protein that would probably be rapidly degraded in the extracellular space.

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Haplotype associations of three DNA polymorphisms at the human low density lipoprotein receptor gene locus in familial hypercholesterolaemia.

Cited by 29 publications

References 8 publications

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia

Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia

A de novo duplication in the low density lipoprotein receptor gene

A double mutant LDL receptor allele in a Cypriot family with heterozygous familial hypercholesterolemia

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