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Correlations between molecular and clinical data in Huntington's disease and implications for predictive testing

Published online by Cambridge University Press:  18 September 2015

S. Claes
Affiliation:
Centrum voor Menselijke Erfelijkheid, K.U. Leuven
M. Decruyenaere
Affiliation:
Centrum voor Menselijke Erfelijkheid, K.U. Leuven
R. Dom
Affiliation:
Departement Neurologie, K.U. Leuven
M. Malfroid
Affiliation:
Universitair Psychiatrisch Centrum, St. Camillus, Bierbeek
G. Evers-Kiebooms
Affiliation:
Centrum voor Menselijke Erfelijkheid, K.U. Leuven
F. Baro
Affiliation:
Universitair Psychiatrisch Centrum, St. Camillus, Bierbeek
J. Godderis
Affiliation:
Departement Psychiatrie, K.U. Leuven
J-P. Fryns
Affiliation:
Centrum voor Menselijke Erfelijkheid, K.U. Leuven
J-J. Cassiman*
Affiliation:
Centrum voor Menselijke Erfelijkheid, K.U. Leuven
*
Centrum voor Menselijke Erfelijkheid, Campus Gasthuisberg, O&N6, Herestraat 49, B-3000 Leuven

Summary

Huntington's disease (HD) is an autosomal dominant disorder of the central nervous system, characterised by neurological, cognitive and psychiatric pathology. Recently the causative genetic defect was discovered. We present a retrospective study of 59 HD patients, investigating correlations between molecular and clinical data.

The correlation between CAG-repeatlength and age at onset is confirmed. No correlations between this biological marker and other clinical features are found (symptoms at onset, mode of progression of the disease).

The consequences of these findings for predictive testing are discussed. Furthermore, a short overview of the predictive testing procedure in the Center for Human Genetics in Leuven (Belgium) is given.

Type
Research Article
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 1995

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References

Literatuur

1.Gusella, J, Wexler, N, Conneally, P, et al.A polymorphic DNA marker genetically linked to Huntington's disease. Nature 1983; 306: 234–8.CrossRefGoogle ScholarPubMed
2.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: 971–83.CrossRefGoogle Scholar
3.Hoogeveen, A, Willemsen, R, Meyer, N, et al.Characterization and localization of the Huntington disease gene product. Hum mol Genet 1993; 2: 2067–73.CrossRefGoogle ScholarPubMed
4.Andrew, S, Goldberg, P, Kremer, B, et al.The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nature Genet 1993; 4: 398403.CrossRefGoogle ScholarPubMed
5.Duyao, M, Ambrose, C, Myers, R, et al.Trinucleotide repeat length instability and age of onset in Huntington's disease. Nature Genet 1993; 4: 387–92.CrossRefGoogle ScholarPubMed
6.Snell, R, MacMillan, J, Cheadle, J, et al.Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nature Genet 1993, 4: 393–97.CrossRefGoogle ScholarPubMed
7.Kremer, B, Goldberg, P, Andrew, S, et al.A worldwide study of the Huntington's disease mutation. New England J Med 1994; 20:1401–6.CrossRefGoogle Scholar
8.Andrew, S, Goldberg, P, Kremer, B, et al.The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nature Genet 1993; 4:398403.CrossRefGoogle ScholarPubMed
9.Legius, E, Cuppens, H, Dierick, H, et al.Limited Expansion of the (CAG)n Repeat of the Huntington Gene: A Premutation (?). Eur J hum Genet 1994; 2: 4450.CrossRefGoogle ScholarPubMed
10.Norremolle, A, Riess, O, Epplen, J, et al.Trinucleotide repeat elongation in the Huntington gene in Huntington disease patients from 71 Danish families. Hum mol Genet 1993; 2:1475–6.CrossRefGoogle ScholarPubMed
11.Stine, O, Pleasant, N, Franz, M, et al.Correlation between the onset age of Huntington's disease and the length of the trinucleotiderepeat in IT-15. Hum mol Genet 1993; 2:1547–9.CrossRefGoogle Scholar
12.Telenius, H, Kremer, H, 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;2:1535–40.CrossRefGoogle ScholarPubMed
13.Duyao, M, Ambrose, C, Myers, R, et al.Trinucleotide repeat length instability and age of onset in Huntington's disease. Nature Genet 1993; 4:387–92.CrossRefGoogle ScholarPubMed
14.Myers, R, Macdonald, M, Koroshetz, W, et al.De novo expansion of a (CAG)n repeat in sporadic Huntington's disease. Nature Genet 1993;5:168–73.CrossRefGoogle ScholarPubMed
15.Macmillan, J, Snell, R, Tyler, A, et al.Molecular analysis and clinical correlation of the Huntington's disease mutation. Lancet 1993, 342: 954–8.CrossRefGoogle ScholarPubMed
16.Di Maio, L, Squitieri, F, Napolitano, G, et al.Onset symptoms in 510 patients with Huntington's disease. J med Genetics 1993; 30:289–92.CrossRefGoogle ScholarPubMed
17.Hayden, MR. Huntington's chorea. Berlin: Springer Verlag, 1981.CrossRefGoogle ScholarPubMed
18.Pflanz, S, Besson, J, Ebmeier, K, et al.The clinical manifestation of mental disorder in Huntington's disease: a retrospective case study of disease progression. Acta psychiat scand 1991; 83:5360.CrossRefGoogle Scholar
19.Read, A. Huntington's disease: testing the test. Nature Genet 1993; 4:329–30.CrossRefGoogle ScholarPubMed
20.Telenius, H, Kremer, B, Goldberg, P, et al.Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nature Genet 1994; 6:409–14.CrossRefGoogle ScholarPubMed
21.Jansen, G, Willems, P, Coerwinkel, M, et al.Gonosomal mosaicism in myotonic dystrophy patients: involvement of mitotic events in (CTG)n repeat variation and selection against extreme expansion in sperm. Am J hum Genet 1994; 54:575–85.Google ScholarPubMed
22.Guidelines for the molecular genetics predictive test in Huntington's disease. Neurology 1994; 44:1533–6.CrossRefGoogle Scholar