Trinucleotide repeat length instability and age of onset in Huntington's disease

M. Duyao; C. Ambrose; R. Myers; A. Novelletto; F. Persichetti; M. Frontali; S. Folstein; C. Ross; M. Franz; M. Abbott; J. Gray; P. Conneally; A. Young; J. Penney; Z. Hollingsworth; I. Shoulson; A. Lazzarini; A. Falek; W. Koroshetz; D. Sax; E. Bird; J. Vonsattel; E. Bonilla; J. Alvir; J. Bickham Conde; J. H. Cha; L. Dure; F. Gomez; M. Ramos; J. Sanchez-Ramos; S. Snodgrass; M. De-Young; N. Wexler; C. Moscowitz; G. Penchaszadeh; H. Macfarlane; M. Anderson; B. Jenkins; J. Srinidhi; G. Barnes; J. Gusella; M. Macdonald

doi:10.1038/ng0893-387

Trinucleotide repeat length instability and age of onset in Huntington's disease

M. Duyao, C. Ambrose, R. Myers, A. Novelletto, F. Persichetti, M. Frontali, S. Folstein, C. Ross, M. Franz, M. Abbott, J. Gray, P. Conneally, A. Young, J. Penney, Z. Hollingsworth, I. Shoulson, A. Lazzarini, A. Falek, W. Koroshetz, D. SaxE. Bird, J. Vonsattel, E. Bonilla, J. Alvir, J. Bickham Conde, J. H. Cha, L. Dure, F. Gomez, M. Ramos, J. Sanchez-Ramos, S. Snodgrass, M. De-Young, N. Wexler, C. Moscowitz, G. Penchaszadeh, H. Macfarlane, M. Anderson, B. Jenkins, J. Srinidhi, G. Barnes, J. Gusella, M. Macdonald

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Abstract

The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37–86 repeat units, whereas normal chromosomes displayed 11–34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.

Original language	English
Pages (from-to)	387-392
Number of pages	6
Journal	Nature Genetics
Volume	4
Issue number	4
DOIs	https://doi.org/10.1038/ng0893-387
Publication status	Published - Aug 1993
Externally published	Yes

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Duyao, M., Ambrose, C., Myers, R., Novelletto, A., Persichetti, F., Frontali, M., Folstein, S., Ross, C., Franz, M., Abbott, M., Gray, J., Conneally, P., Young, A., Penney, J., Hollingsworth, Z., Shoulson, I., Lazzarini, A., Falek, A., Koroshetz, W., ... Macdonald, M. (1993). Trinucleotide repeat length instability and age of onset in Huntington's disease. Nature Genetics, 4(4), 387-392. https://doi.org/10.1038/ng0893-387

@article{bb1408b3cb6348c8b4ca9cb1eff0c019,

title = "Trinucleotide repeat length instability and age of onset in Huntington's disease",

abstract = "The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37–86 repeat units, whereas normal chromosomes displayed 11–34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.",

author = "M. Duyao and C. Ambrose and R. Myers and A. Novelletto and F. Persichetti and M. Frontali and S. Folstein and C. Ross and M. Franz and M. Abbott and J. Gray and P. Conneally and A. Young and J. Penney and Z. Hollingsworth and I. Shoulson and A. Lazzarini and A. Falek and W. Koroshetz and D. Sax and E. Bird and J. Vonsattel and E. Bonilla and J. Alvir and Conde, {J. Bickham} and Cha, {J. H.} and L. Dure and F. Gomez and M. Ramos and J. Sanchez-Ramos and S. Snodgrass and M. De-Young and N. Wexler and C. Moscowitz and G. Penchaszadeh and H. Macfarlane and M. Anderson and B. Jenkins and J. Srinidhi and G. Barnes and J. Gusella and M. Macdonald",

year = "1993",

month = aug,

doi = "10.1038/ng0893-387",

language = "English",

volume = "4",

pages = "387--392",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "4",

}

Duyao, M, Ambrose, C, Myers, R, Novelletto, A, Persichetti, F, Frontali, M, Folstein, S, Ross, C, Franz, M, Abbott, M, Gray, J, Conneally, P, Young, A, Penney, J, Hollingsworth, Z, Shoulson, I, Lazzarini, A, Falek, A, Koroshetz, W, Sax, D, Bird, E, Vonsattel, J, Bonilla, E, Alvir, J, Conde, JB, Cha, JH, Dure, L, Gomez, F, Ramos, M, Sanchez-Ramos, J, Snodgrass, S, De-Young, M, Wexler, N, Moscowitz, C, Penchaszadeh, G, Macfarlane, H, Anderson, M, Jenkins, B, Srinidhi, J, Barnes, G, Gusella, J & Macdonald, M 1993, 'Trinucleotide repeat length instability and age of onset in Huntington's disease', Nature Genetics, vol. 4, no. 4, pp. 387-392. https://doi.org/10.1038/ng0893-387

TY - JOUR

T1 - Trinucleotide repeat length instability and age of onset in Huntington's disease

AU - Duyao, M.

AU - Ambrose, C.

AU - Myers, R.

AU - Novelletto, A.

AU - Persichetti, F.

AU - Frontali, M.

AU - Folstein, S.

AU - Ross, C.

AU - Franz, M.

AU - Abbott, M.

AU - Gray, J.

AU - Conneally, P.

AU - Young, A.

AU - Penney, J.

AU - Hollingsworth, Z.

AU - Shoulson, I.

AU - Lazzarini, A.

AU - Falek, A.

AU - Koroshetz, W.

AU - Sax, D.

AU - Bird, E.

AU - Vonsattel, J.

AU - Bonilla, E.

AU - Alvir, J.

AU - Conde, J. Bickham

AU - Cha, J. H.

AU - Dure, L.

AU - Gomez, F.

AU - Ramos, M.

AU - Sanchez-Ramos, J.

AU - Snodgrass, S.

AU - De-Young, M.

AU - Wexler, N.

AU - Moscowitz, C.

AU - Penchaszadeh, G.

AU - Macfarlane, H.

AU - Anderson, M.

AU - Jenkins, B.

AU - Srinidhi, J.

AU - Barnes, G.

AU - Gusella, J.

AU - Macdonald, M.

PY - 1993/8

Y1 - 1993/8

N2 - The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37–86 repeat units, whereas normal chromosomes displayed 11–34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.

AB - The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37–86 repeat units, whereas normal chromosomes displayed 11–34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.

UR - http://www.scopus.com/inward/record.url?scp=0027240431&partnerID=8YFLogxK

U2 - 10.1038/ng0893-387

DO - 10.1038/ng0893-387

M3 - Article

SN - 1061-4036

VL - 4

SP - 387

EP - 392

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Trinucleotide repeat length instability and age of onset in Huntington's disease

Abstract

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