Nature Genetics
5, 168 - 173 (1993)
doi:10.1038/ng1093-168
De novo expansion of a (CAG)n repeat in sporadic Huntington's diseaseR. H. Myers1, 2, M. E. MacDonald3, W. J. Koroshetz2, M. P. Duyao3, C. M. Ambrose3, S. A. M. Taylor3, G. Barnes3, J. Srinidhi3, C. S. Lin3, W. L. Whaley3, A. M. Lazzarini4, M. Schwarz5, G. Wolff6, E. D. Bird2, 7, J.-P. G. Vonsattel7
& J. F. Gusella3
1Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
2Department of Neurology and Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
3Department of Molecular Neurogenetics Unit, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
4Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA
5Neurologische Klinik, Rheinisch-Westfalische Technische Hochschule Aachen, Germany
6Institut fur Humangenetik und Anthropologie, Albert-Ludwigs-Universitat, Freiburg, Germany
7Brain Tissue Resource Center, Ralph Lowell Laboratory, Mailman Research Center, McLean Hospital, Belmont, Massachusetts 02172, USA Huntington's disease (HD) chromosomes contain an expanded unstable (CAG)n repeat in chromosome 4p16.3. We have examined nine families with potential de novo expression of the disease. With one exception, all of the affected individuals had 42 or more repeat units, well above the normal range. In four families, elderly unaffected relatives inherited the same chromosome as that containing the expanded repeat in the proband, but had repeat lengths of 34−38 units, spanning the gap between the normal and HD distributions. Thus, mutation to HD is usually associated with an expansion from an already large repeat.
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