What is the clinical utility of DNA testing in patients with familial hypercholesterolaemia?

Current Opinion in Lipidology

Volumn 19, Issue 4, 2008, Pages 362-368

  Humphries, Steve E ^a   Norbury, Gail ^b   Leigh, Sarah ^a   Hadfield, S Gaye ^a   Nair, Devikair ^c  

^a ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

^b GREAT ORMOND STREET HOSPITAL   (United Kingdom)

^c ROYAL FREE HOSPITAL   (United Kingdom)

Author keywords

Clinical utility; Familial hypercholesterolaemia; Genetic testing; Mutation analysis

Indexed keywords

DNA; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL;

CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; DNA SCREENING; FAMILIAL HYPERCHOLESTEROLEMIA; GENE MUTATION; GENETIC VARIABILITY; HUMAN; INTRON; ISCHEMIC HEART DISEASE; LABORATORY DIAGNOSIS; LIFESTYLE; NONHUMAN; PRIORITY JOURNAL; RELATIVE; REVIEW; GENETIC PREDISPOSITION; GENETIC SCREENING; GENETICS; HYPERLIPOPROTEINEMIA TYPE 2; MUTATION; PROGNOSIS;

GENETIC PREDISPOSITION TO DISEASE; GENETIC SCREENING; HUMANS; HYPERLIPOPROTEINEMIA TYPE II; MUTATION; PROGNOSIS;

EID: 53149146015     PISSN: 09579672     EISSN: None     Source Type: Journal    
DOI: 10.1097/MOL.0b013e32830636e5     Document Type: Review

References (34)

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4. Humphries SE, Whittall RA, Hubbart CS, et al. Genetic causes of FH in UK patients: relation to plasma lipid levels and coronary heart disease risk. J Med Genet 2006; 43:943-949. Used SSCP for a partial screen of LDLR mutation hot-spot exons and all of the PCSK9 gene in 409 patients with DFH. Detection rate overall 62%, 84 different molecular causes. Significantly higher risk (1.84) of CHD in those with any LDLR mutation, and extreme risk (>19-fold) in PCSK9 p. D374Y carriers, independent of untreated LDL-C levels.
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16. 0 UTR) (two patients) no evidence for causing familial hypercholesterolaemia, 1060+39G>C (two patients) not likely to influence splicing. I377I C>T(exon 9, one patient) and N619N (two patients) and N604N (two patients) are unlikely to cause familial hypercholesterolaemia. Computer prediction of mutations listed in table 4 suggests that G314R (three patients) is unlikely to be pathogenic; however, the c.940C>A responsible for G314R does disrupt the exon/intron 6 splice junction. Overall, this reduces the detection rate to 91 LDLR +12 APOB=39%.
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18. •] (Table 1), is shown in this and other studies to be allelic with other clearly pathogenic variants, in this case with W-18X.
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31. •] (Table 1) are not shown here as allelic with W-18X.
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