Recent advances in genetic testing for familial hypercholesterolemia

Expert Review of Molecular Diagnostics

Volumn 17, Issue 7, 2017, Pages 641-651

  Iacocca, Michael A ^a   Hegele, Robert A ^a  

^a WESTERN UNIVERSITY   (Canada)

Author keywords

copy number variation; coronary heart disease; disease registries; DNA variant; genetic risk score; LDL cholesterol; Monogenic; next generation sequencing; pathogenicity; polygenic

Indexed keywords

DNA; LOW DENSITY LIPOPROTEIN CHOLESTEROL;

CHOLESTEROL BLOOD LEVEL; COPY NUMBER VARIATION; DNA DETERMINATION; DNA HYBRIDIZATION; DNA SEQUENCE; FAMILIAL HYPERCHOLESTEROLEMIA; GENETIC SCREENING; GENOTYPE; HUMAN; MOLECULAR DIAGNOSIS; MOLECULAR GENETICS; MULTIFACTORIAL INHERITANCE; NEXT GENERATION SEQUENCING; PATHOGENICITY; PATIENT CARE; REVIEW; SANGER SEQUENCING; GENETIC PREDISPOSITION; GENETICS; HIGH THROUGHPUT SEQUENCING; MUTATION; SINGLE NUCLEOTIDE POLYMORPHISM;

DNA COPY NUMBER VARIATIONS; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; HYPERLIPOPROTEINEMIA TYPE II; MUTATION; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 85021236188     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1080/14737159.2017.1332997     Document Type: Review

References (53)

1. Wiegman A, Gidding SS, Watts GF, et al. Familial hypercholesterolaemia in children and adolescents:gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36:2425–2437.
2. Benn M, Watts GF, Tybjærg-Hansen A, et al. Mutations causative of familial hypercholesterolaemia:screening of 98 098 individuals from the copenhagen general population study estimated a prevalence of 1 in 217. Eur Heart J. 2016;37:1384–1394.
3. Abul-Husn NS, Manickam K, Jones LK, et al. Genetic identification of familial hypercholesterolemia within a single U.S. health care system. Science. 2016;354:aaf7000.
4. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population:guidance for clinicians to prevent coronary heart disease:consensus statement of the european atherosclerosis society. Eur Heart J. 2013;34:3478–3490.
5. Cuchel M, Bruckert E, Ginsberg HN, et al. Homozygous familial hypercholesterolaemia:new insights and guidance for clinicians to improve detection and clinical management. A position paper from the consensus panel on familial hypercholesterolaemia of the european atherosclerosis society. Eur Heart J. 2014;35:2146–2157.
6. Valle D, Beaudet AL, Vogelstein B, et al. The online metabolic and molecular bases of inherited disease. 8thed. New York:McGraw-Hill Professional; 2000.
7. Versmissen J, Oosterveer DM, Yazdanpanah M, et al. Efficacy of statins in familial hypercholesterolaemia:a long term cohort study. BMJ. 2008;337:a2423.
8. Reiner Ž. Management of patients with familial hypercholesterolaemia. Nat Rev Cardiol. 2015;12:565–575.
9. Gidding SS, Ann Champagne M, de Ferranti SD, et al. The agenda for familial hypercholesterolemia. Circulation. 2015;132:2167–2192.• An in-depth, comprehensive review on familial hypercholesteromia and its clinical management.
10. Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific steering committee on behalf of the simon broome register group. BMJ. 1991;303:893–896.
11. van Aalst-Cohen ES, Jansen ACM, Tanck MWT, et al. Diagnosing familial hypercholesterolaemia:the relevance of genetic testing. Eur Heart J. 2006;27:2240–2246.
12. Genest J, Hegele RA, Bergeron J, et al. Canadian cardiovascular society position statement on familial hypercholesterolemia. Can J Cardiol. 2014;30:1471–1481.
13. Burke AC, Dron JS, Hegele RA, et al. PCSK9:regulation and target for drug development for dyslipidemia. Annu Rev Pharmacol Toxicol. 2017;57:223–244.
14. Soutar AK, Naoumova RP., Mechanisms of disease:genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med. 2007;4:214–225.
15. Humphries SE, Whittall RA, Hubbart CS, et al. 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.
16. Talmud PJ, Shah S, Whittall R, et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia:a case-control study. Lancet. 2013;381:1293–1301.
17. Futema M, Plagnol V, Li K, et al. Whole exome sequencing of familial hypercholesterolaemia patients negative for LDLR/APOB/PCSK9 mutations. J Med Genet. 2014;51:537–544.
18. Futema M, Shah S, Cooper JA, et al. Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries. Clin Chem. 2015;61:231–238.
19. Wang J, Dron JS, Ban MR, et al. Polygenic versus monogenic causes of hypercholesterolemia ascertained clinically. Arterioscler Thromb Vasc Biol. 2016;36:2439–2445.• Extends the routine diagnosis of FH to include CNV analysis and polygenic scores to further increase the number of moleculary defined cases.
20. Kindt I, Mata P, Knowles JW., The role of registries and genetic databases in familial hypercholesterolemia. Curr Opin Lipidol. 2017;28:152–160.•• Highlights the shortcomings of current clinical-based diagnostic scoring criteria, and the advantages of obtaining a molecular diagnosis.
21. Pérez de Isla L, Alonso R, Mata N, et al. Coronary heart disease, peripheral arterial disease, and stroke in familial hypercholesterolaemia. Arterioscler Thromb Vasc Biol. 2016;36:2004–2010.
22. deGoma EM, Ahmad ZS, O’Brien EC, et al. Treatment gaps in adults with heterozygous familial hypercholesterolemia in the United States:CASCADE-FH Registry. Circ Cardiovasc Genet. 2016;9:240–249.• Reports on the low incidence of genetic testing for FH in the USA.
23. Williams RR, Hunt SC, Schumacher MC, et al. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol. 1993;72:171–176.
24. Hopkins PN., Genotype-guided diagnosis in familial hypercholesterolemia:population burden and cascade screening. Curr Opin Lipidol. 2017;28:136–143.
25. Galema-Boers JMH, Versmissen J, Roeters van Lennep HWO, et al. Cascade screening of familial hypercholesterolemia must go on. Atherosclerosis. 2015;242:415–417.•• Example of how effective a nationally implemented cascade screening program can be in identifying FH cases and initiating timely treatment.
26. Bell DA, Pang J, Burrows S, et al. Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical service:an Australian experience. Atherosclerosis. 2015;239:93–100.
27. Jannes CE, Santos RD, de Souza Silva PR, et al. Familial hypercholesterolemia in Brazil:cascade screening program, clinical and genetic aspects. Atherosclerosis. 2015;238:101–107.
28. Tp L, Finborud TH, Manshaus TE, et al. Diagnosis of familial hypercholesterolemia in general practice using clinical diagnostic criteria or genetic testing as part of cascade genetic screening. Public Health Genomics. 2008;11:26–35.
29. Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B):a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385:341–350.
30. Khera AV, Won -H-H, Peloso GM, et al. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67:2578–2589.
31. Andersen L, Estrella L, Andersen R. LDLR variant databases and familial hypercholesterolemia population studies. J Am Coll Cardiol. 2017;69:754–755.
32. Santos RD, Gidding SS, Hegele RA, et al. Defining severe familial hypercholesterolaemia and the implications for clinical management:a consensus statement from the international atherosclerosis society severe familial hypercholesterolemia panel. Lancet Diabetes Endocrinol. 2016;4:850–861.
33. Sjouke B, Tanck MWT, Fouchier SW, et al. Children with hypercholesterolemia of unknown cause:value of genetic risk scores. J Clin Lipidol. 2016;10:851–859.
34. Yuan G, Wang J, Hegele RA. Heterozygous familial hypercholesterolemia:an underrecognized cause of early cardiovascular disease. Cmaj. 2006;174:1124–1129.
35. Umans-Eckenhausen MAW, Defesche JC, van Dam MJ, et al. Long-term compliance with lipid-lowering medication after genetic screening for familial hypercholesterolemia. Arch Intern Med. 2003;163:65–68.
36. Wald DS, Bestwick JP, Morris JK, et al. Child-parent familial hypercholesterolemia screening in primary care. N Engl J Med. 2016;375:1628–1637.
37. Farhan SMK, Hegele RA. Sequencing:the next generation - what is the role of whole-exome sequencing in the diagnosis of familial cardiovascular diseases? Can J Cardiol. 2014;30:152–154.
38. Farhan SMK, Hegele RA. Exome sequencing:new insights into lipoprotein disorders. Curr Cardiol Rep. 2014;16:507.
39. Johansen CT, Dube JB, Loyzer MN, et al. LipidSeq:a next-generation clinical resequencing panel for monogenic dyslipidemias. J Lipid Res. 2014;55:765–772.
40. Kathiresan S, Willer CJ, Peloso GM, et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet. 2009;41:56–65.
41. Teslovich TM, Musunuru K, Smith AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466:707–713.
42. Willer CJ, Schmidt EM, Sengupta S, et al. Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013;45:1274–1283.
43. Alves AC, Etxebarria A, Soutar AK, et al. Novel functional APOB mutations outside LDL-binding region causing familial hypercholesterolaemia. Hum Mol Genet. 2014;23:1817–1828.
44. Green RC, Goddard KAB, Jarvik GP, et al. Clinical sequencing exploratory research consortium:accelerating evidence-based practice of genomic medicine. Am J Hum Genet. 2016;98:1051–1066.
45. Landrum MJ, Lee JM, Riley GR, et al. ClinVar:public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014;42:D980–5.• An excellent variant repository resource for diagnostic laboratories and clinicians to become familiar with.
46. Harrison SM, Dolinsky JS, Knight Johnson AE, et al. Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar. Genet Med. 2017. DOI:10.1038/gim.2017.14.
47. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants:a joint consensus recommendation of the american college of medical genetics and genomics and the association for molecular pathology. Genet Med. 2015;17:405–424.• The guidelines in place to promote more rigorous and standardized variant classification, which are currently being adapted to FH variants specifically.
48. Bourbon M, Alves AC, Sijbrands EJ. Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia. Curr Opin Lipidol. 2017;28:120–129.•• By applying ACMG guidelines to existing documented FH variants, the inadequacy of previous variant classification is highlighted.
49. Lehrman MA, Schneider WJ, Südhof TC, et al. Mutation in LDL receptor:alu-alu recombination deletes exons encoding transmembrane and cytoplasmic domains. Science. 1985;227:140–146.
50. Hobbs HH, Brown MS, Russell DW, et al. Deletion in the gene for the low-density lipoprotein receptor in a majority of French Canadians with familial hypercholesterolemia. N Engl J Med. 1987;317:734–737.
51. Wang J, Ban MR, Hegele RA. Multiplex ligation-dependent probe amplification of LDLR enhances molecular diagnosis of familial hypercholesterolemia. J Lipid Res. 2005;46:366–372.
52. Ahmad A, Iqbal MA. Significance of genome-wide analysis of copy number alterations and UPD in myelodysplastic syndromes using combined CGH - SNP arrays. Curr Med Chem. 2012;19:3739–3747.
53. Bennet AM, Di Angelantonio E, Ye Z, et al. Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA. 2007;298:1300–1311.