Autosomal recessive cerebellar ataxia with oculomotor apraxia (ataxia-telangiectasia-like syndrome) is linked to chromosome 9q34

Ataxia with oculomotor apraxia (ataxia-telangiectasia-like syndrome [AOA]; MIM 208920) is an autosomal recessive disorder characterized by ataxia, ocu lomotor apraxia, and choreoathetosis. These neurological features resemble those of ataxia-telangiectasia (AT), bur in AOA there are none of the extra neurological features of AT, such as immunodeficiency, neoplasia, chromosom al instability, or sensitivity to ionizing radiation, It is unclear whether these patients have a true disorder of chromosomal instability or a primar y neurodegenerative syndrome, and it has not been possible to identify the defective gene in AOA, since the families have been too small for linkage a nalysis. We have identified a new family with AOA, and we show that the pat ients have no evidence of chromosomal instability or sensitivity to ionizin g radiation, suggesting that AOA in this family is a true primary cerebella r ataxia. We have localized the disease gene, by linkage analysis and homoz ygosity mapping, to a 15.9-cM interval on chromosome 3q34, This work will u ltimately allow the disease gene to be identified and its relevance to othe r types of autosomal recessive cerebellar ataxias to be determined.