Abstract
Huntington’s disease (HD) is an autosomal dominant disorder with choreic movements, psychiatric manifestations and cognitive dysfunction. Recently the IT15 gene on chromosome 4p has been identified containing an unstable and expanded trinucleotide repeat in patients with HD. We report on the characteristics of this repeat in 248 individuals from 41 Belgian HD families. The length of the expanded repeat was defined precisely and reproducibly on an ALF sequencer and correlated well with the age of onset (r = −0.72). Paternal transmission of the expanded repeat resulted on average in a significantly longer repeat length (+2.79 repeats) than maternal transmission (−0.29 repeats). (CAG)n repeat of a premutation (?) size was observed in this population with subsequent expansion in the disease range. Presymptomatic or prenatal testing using only linked markers may be problematic in these cases.
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Acknowledgements
The authors would like to express their gratitude to the HD families and to the Belgian HD League for the fruitful collaboration. The expertise and essential assistance of Andrea Boogaerts and Trees Cloostermans in gathering family information and samples is gratefully acknowledged. We would also like to thank Katrien Van den Bosch, Fabienne Rans and Mariëlle Braeken for expert technical assistance and R. Vlietinck for helpful discussion of the statistical aspects. This work was supported by the Interuniversity Network for Fundamental Research sponsored by the Belgian Government (1991–1995).
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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 2, 44–50 (1994). https://doi.org/10.1159/000472340
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DOI: https://doi.org/10.1159/000472340
