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. 1997 Oct;61(4):899–908. doi: 10.1086/514876

Chorea-acanthocytosis: genetic linkage to chromosome 9q21.

J P Rubio 1, A Danek 1, C Stone 1, R Chalmers 1, N Wood 1, C Verellen 1, X Ferrer 1, A Malandrini 1, G M Fabrizi 1, M Manfredi 1, J Vance 1, M Pericak-Vance 1, R Brown 1, G Rudolf 1, F Picard 1, E Alonso 1, M Brin 1, A H Németh 1, M Farrall 1, A P Monaco 1
PMCID: PMC1715977  PMID: 9382101

Abstract

Chorea-acanthocytosis (CHAC) is a rare autosomal recessive disorder characterized by progressive neurodegeneration and unusual red-cell morphology (acanthocytosis), with onset in the third to fifth decade of life. Neurological impairment with acanthocytosis (neuroacanthocytosis) also is seen in abetalipoproteinemia and X-linked McLeod syndrome. Whereas the molecular etiology of McLeod syndrome has been defined (Ho et al. 1994), that of CHAC is still unknown. In the absence of cytogenetic rearrangements, we initiated a genomewide scan for linkage in 11 families, 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 GATA89a11 and D9S1843. A maximum two-point LOD score of 7.1 (theta = .00) for D9S1867 was achieved, and the linked region has been confirmed by homozygosity-by-descent, in offspring from inbred families. These findings provide strong evidence for the involvement of a single locus for CHAC and are the first step in positional cloning of the disease gene.

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Selected References

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