CHOREA-ACANTHOCYTOSIS - GENETIC-LINKAGE TO CHROMOSOME 9Q21

Chorea-acanthocytosis (CHAC) is a rare autosomal recessive disorder ch aracterized by progressive neurodegeneration and unusual red-cell morp hology (acanthocytosis), with onset in the third to fifth decade of li fe. Neurological impairment with acanthocytosis (neuroacanthocytosis) also is seen in abetalipoproteinemia and X-linked McLeod syndrome. Whe reas the molecular etiology of McLeod syndrome has been defined (Ho et al. 1994), that of CHAC is still unknown. In the absence of cytogenet ic rearrangements, we initiated a genomewide scan for linkage in 11 fa milies, segregating for CHAC, who are of diverse geographical origin. We report here that the disease is linked, in all families, to a 6-cM region of chromosome 9q21 that is flanked by the recombinant markers G ATA89a11 and D9S1843. A maximum two-point LOD score of 7.1 (theta = .0 0) for D9S1867 was achieved, and the linked region has been confirmed by homozygosity-by-descent, in offspring from inbred families. These f indings provide strong evidence for the involvement of a single locus for CHAC and are the first step in positional cloning of the disease g ene.