Novel locus for benign hereditary chorea with adult onset maps to chromosome 8q21.3 q23.3

Brain. 2007 Sep;130(Pt 9):2302-9. doi: 10.1093/brain/awm036. Epub 2007 Apr 2.

Abstract

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 (theta = 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)'.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Chorea / diagnostic imaging
  • Chorea / genetics*
  • Chorea / pathology
  • Chromosome Mapping
  • Chromosomes, Human, Pair 8 / genetics*
  • Female
  • Genetic Linkage
  • Humans
  • Lod Score
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Pedigree
  • Tomography, X-Ray Computed