Benign hereditary chorea of early onset maps to chromosome 14q

Abstract

Benign hereditary chorea (BHC) is an autosomal dominant disorder characterized by an early-onset nonprogressive chorea. The early onset and the benign course distinguishes BHC from the more common Huntington disease (HD). Previous studies on families with BHC have shown that BHC and HD are not allelic. We studied a large Dutch kindred with BHC and obtained strong evidence for linkage between the disorder and markers on chromosome 14q (maximum LOD score 6.32 at recombination fraction 0). The BHC locus in this family was located between markers D14S49 and D14S1064, a region spanning approximately 20.6 cM that contains several interesting candidate genes involved in the development and/or maintenance of the CNS: glia maturation factor-beta, GTP cyclohydrolase 1 and the survival of motor neurons (SMN)-interacting protein 1. The mapping of the BHC locus to 14q is a first step toward identification of the gene involved, which might, subsequently, shed light on the pathogenesis of this and other choreatic disorders.

Figure 1

Pedigree of Dutch BHC family with haplotypes for chromosome 14q12–q22 markers (ordered from centromere to telomere). Blackened symbols represent affected subjects. Symbols with N represent unaffected subjects. ? = diagnosis unknown. Bars next to haplotypes indicate a shared-risk haplotype. Blackened circles (•) indicate inconsistent genotype (subject IV-3).

Figure 2

Haplotype sharing of subjects of the Dutch BHC family. Dark bars represent maximal extension of BHC “risk” haplotype in each subject. Dotted lines delineate the maximal critical region of 20.6 cM from recombinational events. Chromosome 14q12–q22 linkage map plus intermarker distances are indicated. A = affected; NA = nonaffected; ? = diagnosis unknown.