Németh A H, Bochukova E, Dunne E, Huson S M, Elston J, Hannan M A, Jackson M, Chapman C J, Taylor A M
Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom.
Am J Hum Genet. 2000 Nov;67(5):1320-6. doi: 10.1016/S0002-9297(07)62962-0. Epub 2000 Oct 5.
Ataxia with oculomotor apraxia (ataxia-telangiectasia-like syndrome [AOA]; MIM 208920) is an autosomal recessive disorder characterized by ataxia, oculomotor apraxia, and choreoathetosis. These neurological features resemble those of ataxia-telangiectasia (AT), but in AOA there are none of the extraneurological features of AT, such as immunodeficiency, neoplasia, chromosomal instability, or sensitivity to ionizing radiation. It is unclear whether these patients have a true disorder of chromosomal instability or a primary neurodegenerative syndrome, and it has not been possible to identify the defective gene in AOA, since the families have been too small for linkage analysis. We have identified a new family with AOA, and we show that the patients have no evidence of chromosomal instability or sensitivity to ionizing radiation, suggesting that AOA in this family is a true primary cerebellar ataxia. We have localized the disease gene, by linkage analysis and homozygosity mapping, to a 15.9-cM interval on chromosome 9q34. This work will ultimately allow the disease gene to be identified and its relevance to other types of autosomal recessive cerebellar ataxias to be determined.
伴动眼性失用的共济失调(共济失调-毛细血管扩张样综合征[AOA];MIM 208920)是一种常染色体隐性疾病,其特征为共济失调、动眼性失用和舞蹈手足徐动症。这些神经学特征与共济失调-毛细血管扩张症(AT)相似,但在AOA中不存在AT的神经外特征,如免疫缺陷、肿瘤形成、染色体不稳定或对电离辐射敏感。尚不清楚这些患者是否存在真正的染色体不稳定疾病或原发性神经退行性综合征,而且由于家系规模过小无法进行连锁分析,因此尚未能够在AOA中鉴定出缺陷基因。我们鉴定出一个患有AOA的新家系,并表明这些患者没有染色体不稳定或对电离辐射敏感的证据,提示该家系中的AOA是一种真正的原发性小脑共济失调。我们通过连锁分析和纯合性定位,将疾病基因定位于9号染色体q34上一个15.9厘摩的区间。这项工作最终将使疾病基因得以鉴定,并确定其与其他类型常染色体隐性小脑共济失调的相关性。