[P07.150] New Locus for Benign Hereditary Chorea with Adult-Onset Maps to Chromosome 8q22.2-q23.3

Kenju Hara, Takayoshi Shimohata, Sanpei Kazuhiro, Jin-ichi Nunomura, Kuroishi, Japan, Izumi Kawachi, Masato Kanazawa, Kensaku Kasuga, Akinori Miyashita, Ryozo Kuwano, Koichi Hirota, Akita, Japan, Shoji Tsuji, Tokyo, Japan, Osamu Onodera, Masatoyo Nishizawa, Yoshiaki Honma, Niigata, Japan

OBJECTIVE: To identify a novel locus for benign hereditary chorea with adult-onset. BACKGROUND: Dominant inherited chorea is a genetically heterogeneous neurodegenerative disorder including Huntington disease (HD), HD like 1 (HDL1), HD like 2 (HDL2), DRPLA, Spinocerebellar ataxia type 17 (SCA17), and benign hereditary chorea (BHC), some of which are caused by mutations in the TITF-1 gene on chromosome 14. However, the molecular basis of BHC without TITF-1 gene mutations or senile chorea remains to be elucidated. DESIGN/METHODS: We identified two five-generation Japanese families with a new type of autosomal dominant chorea. 21 members (7 affected members and 14 unaffected members) in familyA and 5 members (3 affected members and 2 unaffected members) in family B were enrolled. After excluding several inherited choreas by mutational analyses, a genome-wide linkage analysis was performed using 811 microsatellite markers. RESULTS: All the patients presented slowly progressive choreic movements of the four limbs, trunk, and head with an age at onset ranging from 40 to 66 years (average 54.3), which were markedly improved by haloperidol. Patients also developed reduced muscle tones in their limbs. Neither dementia nor psychiatric symptoms were observed in all the patients. Brain CT or MRI of nine patients showed no atrophy of caudate nuclei. These clinical features resembled those of senile chorea. Genetic testing for HD, HDL1, HDL2, DRPLA, and SCA17 gave normal results. A genome-wide linkage analysis revealed a linkage to chromosome 8q22.2-q23.3 with the maximum cumulative two-point LOD score of 4.74 at D8S1784 ( = 0.00). Haplotype analysis defined the critical region as 13.3 cM (15.1 Mb) flanked by D8S1778 and D8S1139, confirming a novel locus for hereditary chorea. CONCLUSIONS/RELEVANCE: We identified a new type of hereditary chorea and designated this disorder benign hereditary chorea type 2 (BHC2).
Category - Movement Disorders
SubCategory - Hyperkinetic Disorders

Thursday, May 3, 2007 11:30 AM

Poster Sessions: Hyperkinetic Movement Disorders II (11:30 AM-2:30 PM)

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