Verbeek Dineke S
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Cerebellum. 2009 Jun;8(2):104-7. doi: 10.1007/s12311-008-0085-1. Epub 2008 Dec 17.
The spinocerebellar ataxia type 23 locus was identified in 2004 based on linkage analysis in a large, two-generation Dutch family. The age of onset ranged 43-56 years and the phenotype was characterized by a slowly progressive, isolated ataxia. Neuropathological examination revealed neuronal loss in the Purkinje cell layer, dentate nuclei, and inferior olives. Ubiquitin-positive intranuclear inclusions were found in nigral neurons, but were considered to be Marinesco bodies. The disease locus on chromosome 20p13-12.3 was found to span a region of approximately 6 Mb of genomic DNA, containing 97 known or predicted genes. To date, no other families have been described that also map to this SCA locus. Direct sequencing of the coding regions of 21 prioritized candidate genes did not reveal any disease-causing mutation. Apparently, the SCA23 gene is a disease gene with a different function than the genes that have been associated with other known SCA types. Work to elucidate the chromosomal organization of the SCA23 locus will eventually discover the responsible disease gene.
2004年，通过对一个大型的荷兰两代家族进行连锁分析，确定了23型脊髓小脑共济失调（SCA23）的基因座。发病年龄在43至56岁之间，其表型特征为缓慢进展的孤立性共济失调。神经病理学检查显示浦肯野细胞层、齿状核和下橄榄核存在神经元丢失。在黑质神经元中发现了泛素阳性核内包涵体，但被认为是马里内斯科小体。发现位于20号染色体p13 - 12.3上的疾病基因座跨越了约6 Mb的基因组DNA区域，包含97个已知或预测的基因。迄今为止，尚未描述其他也定位于此SCA基因座的家族。对21个优先候选基因的编码区进行直接测序未发现任何致病突变。显然，SCA23基因是一个功能不同于与其他已知SCA类型相关基因的疾病基因。阐明SCA23基因座染色体组织的工作最终将发现致病基因。
