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Zoran Brkanac, MD; Laura Bylenok; Magali Fernandez, MD; Mark Matsushita, BS; Hillary Lipe, NP; John Wolff, BS; David Nochlin, MD; Wendy H. Raskind, MD, PhD; Thomas D. Bird, MD

Arch Neurol. 2002;59:1291-1295.

Background  The autosomal dominant spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders. Although molecular genetic studies have so far implicated 16 loci in the etiology of these diseases, approximately 30% of families with SCAs remain unlinked.

Objectives  To report the location of a gene causing a "pure" autosomal dominant cerebellar ataxia in one family and to describe the clinical phenotype.

Patients  We have identified a 4-generation American family of English and Dutch ethnicity with a pure cerebellar ataxia displaying an autosomal dominant pattern of inheritance. The disease typically has its onset in the third and fourth decades of life, shows no evidence of anticipation, progresses slowly, and does not appear to decrease life expectancy. Clinical DNA testing excluded SCA1, 2, 3, 6, 7, and 8.

Methods  A genome-wide linkage analysis at a 10 centimorgan (cM) level was performed with samples from 26 family members (11 affected, 10 clinically unaffected at risk, and 5 spouses).

Results  Assuming 90% penetrance, we found suggestive evidence of linkage to chromosome 19, with a lod score of 2.49 for D19S571. More detailed mapping in this region provided a maximum 2-point lod score of 2.57 at = 0 for D19S254 and a maximum multipoint lod score of 4.72 at D19S926. By haplotype construction a 22-cM critical region from D19S601 to the q telomere was defined.

Conclusions  We have mapped a gene for an autosomal dominant SCA to chromosome 19q13.4-qter in one family. The critical region overlaps with the locus for SCA14, a disease described in a single Japanese family and characterized by axial myoclonus. Myoclonus was not seen in the family we studied, but it remains possible that the 2 disorders are allelic variants.

From the Departments of Psychiatry (Dr Brkanac), Medicine (Ms Bylenok, Messrs Matsushita and Wolff, and Drs Raskind and Bird), Neurology (Ms Lipe and Dr Bird), and Pathology (Dr Nochlin), University of Washington School of Medicine, Seattle; Department of Medicine, Ohio State University, Columbus (Dr Fernandez); and Geriatric (Ms Lipe and Dr Bird) and VISN 20 Mental Illness (Dr Raskind) Research, Education, and Clinical Centers, Veterans Affairs Puget Sound Health Care System, Seattle.

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