Familial influence on age of onset among siblings with Huntington disease*

Wiley - Tập 105 Số 5 - Trang 399-403 - 2001
Adam Rosenblatt1, Ryan R. Brinkman2, Kung‐Yee Liang3, E. Almqvist2, Russell L. Margolis1, Chiung‐Yu Huang3, M. Sherr1, Mary L. Franz1, Margaret H. Abbott1, Michael R. Hayden2, Christopher A. Ross1
1Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
3Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland

Tóm tắt

Abstract

In order to provide data relevant to a search for modifying genes for age of onset in Huntington disease, we examined the relationship between CAG number and age of onset in a total of 370 individuals from 165 siblingships, in two cohorts of siblings with Huntington disease: an American group of 144 individuals from 64 siblingships, and a Canadian population of 255 individuals from 113 siblingships. Using a logarithmic model to regress the age of onset on the number of CAG triplets, we found that CAG number alone accounted for 65%–71% of the variance in age of onset. The siblingship an individual belonged to accounted for 11%–19% of additional variance. This adds to the previous evidence that there are familial modifiers of the age of onset, independent of the CAG number. Such modifiers may consist of additional genes, which could be the target of a linkage study. A linkage study is feasible with the cooperation of a number of major centers and may be made more efficient by concentrating on sibling pairs that are highly discordant for age of onset. © 2001 Wiley‐Liss, Inc.

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Wiley

Tập 105 Số 5

399-403

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