Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project

Clinical Genetics

Volumn 77, Issue 6, 2010, Pages 572-580

  Taylor, A ^a   Wang, D ^a   Patel, K ^a   Whittall, R ^b   Wood, G ^c   Farrer, M ^c   Neely, R D G ^d   Fairgrieve, S ^d   Nair, D ^c   Barbir, M ^e   Jones, J L ^e   Egan, S ^f   Everdale, R ^f   Lolin, Y ^g   Hughes, E ^h   Cooper, J A ^b   Hadfield, S G ^b   Norbury, G ^a   Humphries, S E ^a  

^a GREAT ORMOND STREET HOSPITAL   (United Kingdom)

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

^c ROYAL FREE HOSPITAL   (United Kingdom)

^d ROYAL VICTORIA INFIRMARY   (United Kingdom)

^e ROYAL BROMPTON AND HAREFIELD NHS FOUNDATION TRUST   (United Kingdom)

^f POOLE HOSPITAL NHS FOUNDATION TRUST   (United Kingdom)

^g MAIDSTONE AND TUNBRIDGE WELLS NHS TRUST   (United Kingdom)

^h SANDWELL GENERAL HOSPITAL   (United Kingdom)

Author keywords

APOB; Familial hypercholesterolaemia; LDLR; Mutation detection; PCSK9

Indexed keywords

APOLIPOPROTEIN B; ARGININE; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; TYROSINE; LOW DENSITY LIPOPROTEIN RECEPTOR;

ARTICLE; ASIAN; ETHNICITY; EXON; GENE MUTATION; GENE SEQUENCE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HYPERCHOLESTEROLEMIA; INDIAN; MAJOR CLINICAL STUDY; PILOT STUDY; PREVENTIVE HEALTH SERVICE; PRIORITY JOURNAL; SINGLE STRAND CONFORMATION POLYMORPHISM; UNITED KINGDOM; GENETIC SCREENING; GENETICS; MUTATION;

APOLIPOPROTEINS B; GENETIC TESTING; GREAT BRITAIN; HUMANS; HYPERCHOLESTEROLEMIA; MUTATION; PILOT PROJECTS; RECEPTORS, LDL;

EID: 77953949143     PISSN: 00099163     EISSN: 13990004     Source Type: Journal    
DOI: 10.1111/j.1399-0004.2009.01356.x     Document Type: Article

References (44)

1. Marks D, Thorogood M, Neil HA, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis 2003, 168:1-14.
2. Marks D, Thorogood M, Farrer JM, Humphries SE. Census of clinics providing specialist lipid services in the United Kingdom. J Public Health (Oxf) 2004, 26:353-354.
3. Betteridge DJ, Broome K, Durrington PN. Mortality in treated heterozygous familial hypercholesterolaemia: implications for clinical management. Atherosclerosis 1999, 142:105-112.
4. Neil A, Cooper J, Betteridge DJ, Capps N, McDowell TL, Durrington P, Seed M, Humphries SE. Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study. Eur Heart J 2008, 29:2625-2633.
5. Versmissen J, Oosterveer DM, Yazdanpanah M. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ 2008, 337:a2423.
6. DeMott K, Nherera L, Shaw EJ. Clinical Guidelines and Evidence Review for Familial Hypercholesterolaemia: the identification and management of adults and children with familial hypercholesterolaemia 2008, London, National Collaborating Centre for Primary Care and Royal College of General Practitioners
7. Wierzbicki AS, Humphries SE, Minhas R. Familial hypercholesterolaemia: summary of NICE guidance. BMJ 2008, 337:a1095.
8. Umans-Eckenhausen MA, Defesche JC, Sijbrands EJ, Scheerder RL, Kastelein JJ. Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands. Lancet 2001, 357:165-168.
9. Leren TP, Manshaus T, Skovholt U. Application of molecular genetics for diagnosing familial hypercholesterolemia in Norway: results from a family-based screening program. Semin Vasc Med 2004, 4:75-85.
10. Pocovi M, Civeira F, Alonso R, Mata P. Familial hypercholesterolemia in Spain: case-finding program, clinical and genetic aspects. Semin Vasc Med 2004, 4:67-74.
11. Bhatnagar D, Morgan J, Siddiq S, Mackness MI, Miller JP, Durrington PN. Outcome of case finding among relatives of patients with known heterozygous familial hypercholesterolaemia. BMJ 2000, 321:1497-1500.
12. Marteau T, Senior V, Humphries SE. Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial. Am J Med Genet A 2004, 128:285-293.
13. Marks D, Thorogood M, Neil SM, Humphries SE, Neil HA. Cascade screening for familial hypercholesterolaemia: implications of a pilot study for national screening programmes. J Med Screen 2006, 13:156-159.
14. Humphries SE, Cranston T, Allen M. Mutational analysis in UK patients with a clinical diagnosis of familial hypercholesterolaemia: relationship with plasma lipid traits, heart disease risk and utility in relative tracing. J Mol Med 2006, 84:203-214.
15. Soutar AK, Naoumova RP. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Natl Clin Pract Cardiovasc Med 2007, 4:214-225.
16. Varret M, Abifadel M, Rabes JP, Boileau C. Genetic heterogeneity of autosomal dominant hypercholesterolemia. Clin Genet 2008, 73:1-13.
17. Saint-Jore B, Varret M, Dachet C. Autosomal dominant type IIa hypercholesterolemia: evaluation of the respective contributions of LDLR and APOB gene defects as well as a third major group of defects. Eur J Hum Genet 2000, 8:621-630.
18. Kathiresan S, Willer CJ, Peloso GM. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 2009, 41:56-65.
19. Leigh SE, Foster AH, Whittall RA, Hubbart CS, Humphries SE. Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database. Ann Hum Genet 2008, 72:485-498.
20. Sun XM, Webb JC, Gudnason V. Characterization of deletions in the LDL receptor gene in patients with familial hypercholesterolemia in the United Kingdom. Arterioscler Thromb 1992, 12:762-770.
21. Taylor A, Martin B, Wang D, Patel K, Humphries SE, Norbury G. Multiplex ligation-dependent probe amplification analysis to screen for deletions and duplications of the LDLR gene in patients with familial hypercholesterolaemia. Clin Genet 2009, 76(1):69-75.
22. Heath KE, Humphries SE, Middleton-Price H, Boxer M. A molecular genetic service for diagnosing individuals with familial hypercholesterolaemia (FH) in the United Kingdom. Eur J Hum Genet 2001, 9:244-252.
23. Bodamer OA, Bercovich D, Schlabach M, Ballantyne C, Zoch D, Beaudet AL. Use of denaturing HPLC to provide efficient detection of mutations causing familial hypercholesterolemia. Clin Chem 2002, 48:1913-1918.
24. Cefalu AB, Barraco G, Noto D, Valenti V, Barbagallo CM, Elisir GD, Cuniberti LA, Werba JP, Librea M, Costa S, Gianguzza F, Notarbartolo A, Travali S, Averna MR. Six novel mutations of the LDL Receptor gene in FH kindred of Sicilian and Paraguayan descent. Int J Mol Med 2006, 17(3):539-546.
25. Humphries SE, Whittall RA, Hubbart CS. Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. J Med Genet 2006, 43:943-949.
26. Laitinen J, Samarut J, Holtta E. A nontoxic and versatile protein salting-out method for isolation of DNA. Biotechniques 1994, 17:316-322.
27. Taylor A, Tabrah S, Wang D. Multiplex ARMS analysis to detect 13 common mutations in familial hypercholesterolaemia. Clin Genet 2007, 71:561-568.
28. Taylor A, Patel K, Tsedeke J, Humphries SE, Norbury G. Mutation screening in patients for familial hypercholesterolaemia (ADH). Clin Genet 2009, PMID: 19843101 [Epub ahead of print].
29. Cotton RG, Scriver CR. Proof of " disease causing" mutation. Hum Mutat 1998, 12:1-3.
30. Hobbs HH, Brown MS, Goldstein JL. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. Hum Mutat 1992, 1:445-466.
31. Hadfield SG, Horara S, Starr BJ. Are patients with familial hypercholesterolaemia well managed in lipid clinics? An audit of eleven clinics from the Department of Health Familial Hypercholesterolaemia Cascade Testing project. Ann Clin Biochem 2008, 45:199-205.
32. Graham CA, McClean E, Ward AJ. Mutation screening and genotype: phenotype correlation in familial hypercholesterolaemia. Atherosclerosis 1999, 147:309-316.
33. Heath KE, Gudnason V, Humphries SE, Seed M. The type of mutation in the low density lipoprotein receptor gene influences the cholesterol-lowering response of the HMG-CoA reductase inhibitor simvastatin in patients with heterozygous familial hypercholesterolaemia. Atherosclerosis 1999, 143:41-54.
34. Bergman A, Flodin A, Engwall Y. A high frequency of germline BRCA1/2 mutations in western Sweden detected with complementary screening techniques. Fam Cancer 2005, 4:89-96.
35. Capalbo C, Ricevuto E, Vestri A. BRCA1 and BRCA2 genetic testing in Italian breast and/or ovarian cancer families: mutation spectrum and prevalence and analysis of mutation prediction models. Ann Oncol 2006, 17((Suppl. 7)):vii34-vii40.
36. Bourbon M, Fowler AM, Sun XM, Soutar AK. Inheritance of two different alleles of the low-density lipoprotein (LDL)-receptor gene carrying the recurrent Pro664Leu mutation in a patient with homozygous familial hypercholesterolaemia. Clin Genet 1999, 56:225-231.
37. Lehrman MA, Goldstein JL, Brown MS, Russell DW, Schneider WJ. Internalization-defective LDL receptors produced by genes with nonsense and frameshift mutations that truncate the cytoplasmic domain. Cell 1985, 41:735-743.
38. Loux N, Benlian P, Pastier D. Recurrent mutation at aa 792 in the LDL receptor gene in a French patient. Hum Genet 1991, 87:373-375.
39. Jensen HK, Jensen LG, Meinertz H, Hansen PS, Gregersen N, Faergeman O. Spectrum of LDL receptor gene mutations in Denmark: implications for molecular diagnostic strategy in heterozygous familial hypercholesterolemia. Atherosclerosis 1999, 146:337-344.
40. Neil HAW, Huxley RR, Hawkins MM. Comparison of the risk of fatal coronary heart disease in treated xanthomatous and non-xanthomatous heterozygous familial hypercholesterolaemia: a prospective registry study. Atherosclerosis 2003, 170:73-78.
41. Hadfield SG, Horara S, Starr BJ. Family tracing to identify patients with Familial Hypercholesterolaemia: the second Audit of the Department of Health Familial Hypercholesterolaemia Cascade Testing Project. Ann Clin Biochem 2009, 46:24-32.
42. Starr B, Hadfield SG, Hutten BA. Development of sensitive and specific age- and gender-specific low-density lipoprotein cholesterol cutoffs for diagnosis of first-degree relatives with familial hypercholesterolaemia in cascade testing. Clin Chem Lab Med 2008, 46:791-803.
43. Blesa S, Garcia-Garcia AB, Martinez-Hervas S. Analysis of sequence variations in the LDL receptor gene in Spain: general gene screening or search for specific alterations? Clin Chem 2006, 52:1021-1025.
44. Wright WT, Heggarty SV, Young IS. Multiplex Mass ARRAY spectrometry (iPLEX) produces a fast and economical test for 56 familial hypercholesterolaemia-causing mutations. Clin Genet 2008, 74:463-468.