Predictive testing for Huntington disease: Interpretation and significance of intermediate alleles

Clinical Genetics

Volumn 70, Issue 4, 2006, Pages 283-294

  Semaka, A ^a   Creighton, S ^b   Warby, S ^a   Hayden, M A ^b  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b CHILDREN S AND WOMEN S HEALTH CENTRE OF BRITISH COLUMBIA   (Canada)

Author keywords

CAG repeat instability; Genetic counselling; Huntington disease; Intermediate alleles; Predictive testing; Psychosocial consequences; Risk assessment; Risk estimates

Indexed keywords

ALLELE; CLINICAL FEATURE; DISEASE ASSOCIATION; FAMILY HISTORY; GENE FREQUENCY; GENE MUTATION; GENE SEQUENCE; GENETIC RISK; GENETIC SCREENING; GENETIC VARIABILITY; GENOMIC INSTABILITY; HAPLOTYPE; HUMAN; HUNTINGTON CHOREA; MUTATIONAL ANALYSIS; PREDICTION; PRIORITY JOURNAL; PSYCHOSOCIAL CARE; REVIEW; RISK ASSESSMENT; RISK FACTOR; SEQUENCE ANALYSIS; TRINUCLEOTIDE REPEAT;

AGE FACTORS; ALLELES; CHILD; FEMALE; HAPLOTYPES; HETEROZYGOTE DETECTION; HUMANS; HUNTINGTON DISEASE; MALE; MOLECULAR DIAGNOSTIC TECHNIQUES; MUTATION; PEDIGREE; RISK; SEX FACTORS; TRINUCLEOTIDE REPEATS;

EID: 33748321965     PISSN: 00099163     EISSN: 13990004     Source Type: Journal    
DOI: 10.1111/j.1399-0004.2006.00668.x     Document Type: Review

References (73)

1. Hayden MR. Huntington's chorea. Berlin; New York: Springer-Verlag, 1981.
2. The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993: 72: 971-983.
3. Kremer B, Goldberg P, Andrew SE et al. A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med 1994: 330: 1401-1406.
4. Langbehn DR, Brinkman RR, Falush D et al. A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length. Clin Genet 2004: 65: 267-277.
5. Brinkman RR, Mezei MM, Theilmann J et al. The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size. Am J Hum Genet 1997: 60: 1202-1210.
6. Duyao M, Ambrose C, Myers R et al. Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat Genet 1993: 4: 387-392.
7. Telenius H, Kremer HP, Theilmann J et al. Molecular analysis of juvenile Huntington disease: The major influence on (CAG)n repeat length is the sex of the affected parent. Hum Mol Genet 1993: 2: 1535-1540.
8. Nance MA, Myers RH. Juvenile onset Huntington's disease: Clinical and research perspectives. Ment Retard Dev Disabil Res Rev 2001: 7: 153-157.
9. Rubinsztein DC, Leggo J, Coles R et al. Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats. Am J Hum Genet 1996: 59: 16-22.
10. McNeil SM, Novelletto A, Srinidhi J et al. Reduced penetrance of the Huntington's disease mutation. Hum Mol Genet 1997: 6: 775-779.
11. The American College of Medical Genetics/American Society of Human Genetics Huntington Disease Genetic Testing Working Group. ACMG/ASHG statement: Laboratory guidelines for Huntington disease genetic testing. Am J Hum Genet 1998: 62: 1243-1247.
12. Myers RH, MacDonald ME, Koroshetz WJ et al. De novo expansion of a (CAG)n repeat in sporadic Huntington's disease. Nat Genet 1993: 5: 168-173.
13. Goldberg YP, Kremer B, Andrew SE et al. Molecular analysis of new mutations for Huntington's disease: Intermediate alleles and sex of origin effects. Nat Genet 1993: 5: 174-179.
14. Almqvist EW, Elterman DS, MacLeod PM et al. High incidence rate and absent family histories in one quarter of patients newly diagnosed with Huntington disease in British Columbia. Clin Genet 2001: 60: 198-205.
15. Bateman D, Boughey AM, Scaravilli F et al. A follow-up study of isolated cases of suspected Huntington's disease. Ann Neurol 1992: 31: 293-298.
16. Goldberg YP, McMurray CT, Zeisler J et al. Increased instability of intermediate alleles in families with sporadic Huntington disease compared to similar sized intermediate alleles in the general population. Hum Mol Genet 1995: 4: 1911-1918.
17. Telenius H, Almqvist E, Kremer B et al. Somatic mosaicism in sperm is associated with intergenerational (CAG)n changes in Huntington disease. Hum Mol Genet 1995: 4: 189-195.
18. Kelly TE, Allinson P, McGlennen RC et al. Expansion of a 27 CAG repeat allele into a symptomatic Huntington disease-producing allele. Am J Med Genet 1999: 87: 91-92.
19. Almqvist E, Andrew S, Theilmann J et al. Geographical distribution of haplotypes in Swedish families with Huntington's disease. Hum Genet 1994: 94: 124-128.
20. Potter NT, Spector EB, Prior TW. Technical standards and guidelines for Huntington disease testing. Genet Med 2004: 6: 61-65.
21. Maat-Kievit A, Losekoot M, Van Den Boer-Van Den Berg H et al. New problems in testing for Huntington's disease: The issue of intermediate and reduced penetrance alleles. J Med Genet 2001: 38: E12.
22. Pearson CE, Edamura KN, Cleary JD. Repeat instability: Mechanisms of dynamic mutations. Nat Rev Genet 2005: 6: 729-742.
23. Cleary JD, Pearson CE. Replication fork dynamics and dynamic mutations: the fork-shift model of repeat instability. Trends Genet 2005: 21: 272-280.
24. Kremer B, Almqvist E, Theilmann J et al. Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes. Am J Hum Genet 1995: 57: 343-350.
25. Giovannone B, Sabbadini G, Di ML et al. Analysis of (CAG)n size heterogeneity in somatic and sperm cell DNA from intermediate and expanded Huntington disease gene carriers. Hum Mutat 1997: 10: 458-464.
26. MacDonald ME, Barnes G, Srinidhi J et al. Gametic but not somatic instability of CAG repeat length in Huntington's disease. J Med Genet 1993: 30: 982-986.
27. Zuhlke C, Riess O, Bockel B et al. Mitotic stability and meiotic variability of the (CAG)n repeat in the Huntington disease gene. Hum Mol Genet 1993: 2: 2063-2067.
28. Chong SS, Almqvist E, Telenius H et al. Contribution of DNA sequence and CAG size to mutation frequencies of intermediate alleles for Huntington disease: Evidence from single sperm analyses. Hum Mol Genet 1997: 6: 301-309.
29. Telenius H, Kremer B, Goldberg YP et al. Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nat Genet 1994: 6: 409-414.
30. Aronin N, Chase K, Young C et al. CAG expansion affects the expression of mutant Huntingtin in the Huntington's disease brain. Neuron 1995: 15: 1193-1201.
31. Kennedy L, Shelbourne PF. Dramatic mutation instability in HD mouse striatum: Does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease? Hum Mol Genet 2000: 9: 2539-2544.
32. Lucotte G, Gerard N, Aouizerate A et al. Patterns of meiotic variability of the (CAG)n repeat in the Huntington disease gene. Genet Couns 1997: 8: 77-81.
33. Goldberg YP, Andrew SE, Theilmann J et al. Familial predisposition to recurrent mutations causing Huntington's disease: Genetic risk to sibs of sporadic cases. J Med Genet 1993: 30: 987-990.
34. Sanchez A, Mila M, Castellvi-Bel S et al. Maternal transmission in sporadic Huntington's disease. J Neurol Neurosurg Psychiatry 1997: 62: 535-537.
35. Laccone F, Christian W. A recurrent expansion of a maternal allele with 36 CAG repeats causes Huntington disease in two sisters. Am J Hum Genet 2000: 66: 1145-1148.
36. Cleary JD, Pearson CE. The contribution of cis-elements to disease-associated repeat instability: Clinical and experimental evidence. Cytogenet Genome Res 2003: 100: 25-55.
37. Cleary JD, Nichol K, Wang YH et al. Evidence of cis-acting factors in replication-mediated trinucleotide repeat instability in primate cells. Nat Genet 2002: 31: 37-46.
38. Squitieri F, Andrew SE, Goldberg YP et al. DNA haplotype analysis of Huntington disease reveals clues to the origins and mechanisms of CAG expansion and reasons for geographic variations of prevalence. Hum Mol Genet 1994: 3: 2103-2114.
39. Rubinsztein DC, Barton DE, Davison BC et al. Analysis of the Huntington gene reveals a trinucleotide-length polymorphism in the region of the gene that contains two CCG-rich stretches and a correlation between decreased age of onset of Huntington's disease and CAG repeat number. Hum Mol Genet 1993: 2: 1713-1715.
40. Rubinsztein DC, Leggo J, Barton DE et al. Site of (CCG) polymorphism in the HD gene. Nat Genet 1993: 5: 214-215.
41. Rubinsztein DC, Leggo J, Goodburn S et al. Haplotype analysis of the delta 2642 and (CAG)n polymorphisms in the Huntington's disease (HD) gene provides an explanation for an apparent 'founder'HD haplotype. Hum Mol Genet 1995: 4: 203-206.
42. Coles R, Leggo J, Rubinsztein DC. Analysis of the 5′ upstream sequence of the Huntington's disease (HD) gene shows six new rare alleles which are unrelated to the age at onset of HD. J Med Genet 1997: 34: 371-374.
43. Andrew SE, Goldberg YP, Theilmann J et al. A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: Implications for diagnostic accuracy and predictive testing. Hum Mol Genet 1994: 3: 65-67.
44. Ambrose CM, Duyao MP, Barnes G et al. Structure and expression of the Huntington's disease gene: Evidence against simple inactivation due to an expanded CAG repeat. Somat Cell Mol Genet 1994: 20: 27-38.
45. Murray A, Macpherson JN, Pound MC et al. The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission. Hum Mol Genet 1997: 6: 173-184.
46. Chung MY, Ranum LP, Duvick LA et al. Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I. Nat Genet 1993: 5: 254-258.
47. Crawford DC, Nickerson DA. Definition and clinical importance of haplotypes. Annu Rev Med 2005: 56: 303-320.
48. Andrew SE, Hayden MR. Origins and evolution of Huntington disease chromosomes. Neurodegeneration 1995: 4: 239-244.
49. Almqvist E, Spence N, Nichol K et al. Ancestral differences in the distribution of the delta 2642 glutamic acid polymorphism is associated with varying CAG repeat lengths on normal chromosomes: Insights into the genetic evolution of Huntington disease. Hum Mol Genet 1995: 4: 207-214.
50. Leeflang EP, Zhang L, Tavare S et al. Single sperm analysis of the trinucleotide repeats in the Huntington's disease gene: Quantification of the mutation frequency spectrum. Hum Mol Genet 1995: 4: 1519-1526.
51. Hayden MR, Bombard Y. Psychosocial effects of predictive testing for Huntington disease. In: Anderson KE, Weiner WJ, Lang AE, eds. Advances in neurology, vol. 96. Philadelphia: Lippincott Williams & Wilkins, 2005: 226-239.
52. Van den Boer-Van den Berg HM, Maat-Kievit AA. The whole truth and nothing but the truth, but what is the truth? J Med Genet 2001: 38: 39-42.
53. International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington's Chorea. Guidelines for the molecular genetics predictive test in Huntington's disease. Neurology 1994: 44: 1533-1536.
54. Maat-Kievit A, Helderman-van den Enden P, Losekoot M et al. Using a roster and haplotyping is useful in risk assessment for persons with intermediate and reduced penetrance alleles in Huntington disease. Am J Med Genet 2001: 105: 737-744.
55. Evers-Kiebooms G, Swerts A, Cassiman JJ et al. The motivation of at-risk individuals and their partners in deciding for or against predictive testing for Huntington's disease. Clin Genet 1989: 35: 29-40.
56. Tibben A, Frets PG, van de Kamp JJ et al. Presymptomatic DNA-testing for Huntington disease: Pretest attitudes and expectations of applicants and their partners in the Dutch program. Am J Med Genet 1993: 48: 10-16.
57. Decruyenaere M, Evers-Kiebooms G, Boogaerts A et al. Predictive testing for Huntington's disease: Risk perception, reasons for testing and psychological profile of test applicants. Genet Couns 1995: 6: 1-13.
58. Bish A, Sutton S, Jacobs C et al. No news is (not necessarily) good news: Impact of preliminary results for BRCA1 mutation searches. Genet Med 2002: 4: 353-358.
59. Fu YH, Kuhl DP, Pizzuti A et al. Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox. Cell 1991: 67: 1047-1058.
60. Conkie-Rosell A, Finucane B, Cronister A et al. Genetic counseling for fragile x syndrome: Updated recommendations of the national society of genetic counselors. J Genet Couns 2005: 14: 249-270.
61. Orr HT, Chung MY, Banfi S et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet 1993: 4: 221-226.
62. Zuhlke C, Dalski A, Hellenbroich Y et al. Spinocerebellar ataxia type 1 (SCA1): Phenotype-genotype correlation studies in intermediate alleles. Eur J Hum Genet 2002: 10: 204-209.
63. Kawaguchi Y, Okamoto T, Taniwaki M et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 1994: 8: 221-228.
64. Stevanin G, Giunti P, Belal GD et al. De novo expansion of intermediate alleles in spinocerebellar ataxia 7. Hum Mol Genet 1998: 7: 1809-1813.
65. Martorell L, Monckton DG, Sanchez A et al. Frequency and stability of the myotonic dystrophy type 1 premutation. Neurology 2001: 56: 328-335.
66. Montermini L, Andermann E, Labuda M et al. The Friedreich ataxia GAA triplet repeat: Premutation and normal alleles. Hum Mol Genet 1997: 6: 1261-1266.
67. Pandolfo M. Friedreich's ataxia: Clinical aspects and pathogenesis. Semin Neurol 1999: 19: 311-321.
68. Nolin SL, Brown WT, Glicksman A et al. Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles. Am J Hum Genet 2003: 72: 454-464.
69. Martorell L, Gamez J, Cayuela ML et al. Germline mutational dynamics in myotonic dystrophy type 1 males: Allele length and age effects. Neurology 2004: 62: 269-274.
70. Abbruzzese C, Costanzi PS, Mariani B et al. Instability of a premutation allele in homozygous patients with myotonic dystrophy type 1. Ann Neurol 2002: 52: 435-441.
71. Cossee M, Schmitt M, Campuzano V et al. Evolution of the Friedreich's ataxia trinucleotide repeat expansion: Founder effect and premutations. Proc Natl Acad Sci U S A 1997: 94: 7452-7457.
72. Igarashi S, Takiyama Y, Cancel G et al. Intergenerational instability of the CAG repeat of the gene for Machado-Joseph disease (MJD1) is affected by the genotype of the normal chromosome: Implications for the molecular mechanisms of the instability of the CAG repeat. Hum Mol Genet 1996: 5: 923-932.
73. Sasaki H, Wakisaka A, Fukazawa T et al. CAG repeat expansion of Machado-Joseph disease in the Japanese: Analysis of the repeat instability for parental transmission, and correlation with disease phenotype. J Neurol Sci 1995: 133: 128-133.