Brain Advance Access published online on April 2, 2007
Brain, doi:10.1093/brain/awm036
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Novel locus for benign hereditary chorea with adult onset maps to chromosome 8q21.3–q23.3
1Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan, 2Department of Neurology, Sado General Hospital, 3Department of Neurology, Kuroishi Municipal Hospital, 4Department of Neurology, Research Institute for Brain and Blood Vessels, Akita, 5Genome Science Branch, Center for Bioresource-Based Research, Niigata University Brain Research Institute, 6Akita Red Cross Blood Center, 7Department of Neurology, University of Tokyo, Graduate School of Medicine, 8Department of Molecular Neuroscience, Resource Branch for Brain Disease Research, Center for Bioresource-Based Researches, Brain Research Institute, Niigata University, Niigata and 9Geriatric Heath Services Facilities "Sado", Japan
Correspondence to:
Masatoyo Nishizawa, MD, PhD, Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahi-machi-dori Niigata, Niigata 951-8585, Japan E-mail: nishi{at}bri.niigata-u.ac.jp
Autosomal dominant choreas are genetically heterogeneous disorders including Huntington disease (HD), Huntington disease like 1 (HDL1), Huntington disease like 2 (HDL2), dentatorubro-pallidoluysian atrophy (DRPLA), spinocerebellar ataxia type 17 (SCA17) and benign hereditary chorea (BHC). We identified two Japanese families with adult-onset benign chorea without dementia inherited in an autosomal dominant pattern. All affected individuals presented slowly progressive choreic movements in their upper and lower extremities, trunk and head with an age of onset ranging from 40 to 66 (average 54.3), which were markedly improved by haloperidol. The affected individuals also developed reduced muscle tones in their extremities. The findings obtained in the brain CT or MRI studies of nine affected individuals were normal. These clinical features resemble those of the so-called ‘senile chorea’. HD, HDL1, HDL2, DRPLA, SCA17 and BHC caused by mutations in the TITF-1 gene were excluded by mutational and linkage analyses. A genome-wide linkage analysis revealed linkage to chromosome 8q21.3–q23.3 with a maximum cumulative two-point log of the odds (LOD) score of 4.74 at D8S1784 (
= 0.00). Haplotype analysis of both the families defined the candidate region as 21.5 Mb interval flanked by M9267 and D8S1139. We named this adult-onset dominant inherited chorea ‘benign hereditary chorea type 2 (BHC2)’.
Key Words: benign hereditary chorea; autosomal dominant inheritance; adult-onset; linkage analysis; chromosome 8q21.3–23.3
Abbreviations: BHC, benign hereditary chorea; HD, Huntington disease; HDL1, Huntington disease like 1; HDL2, Huntington disease like 2; DRPLA, dentatorubral pallidoluysian atrophy; SCA, spinocerebellar ataxia; SPECT, single-photon emission computed tomography
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Received October 28, 2006. Revised February 6, 2007. Accepted February 12, 2007.
*These authors contributed equally to this work.