Storey E, Bahlo M, Fahey M, Sisson O, Lueck C J, Gardner R J M
Department of Neuroscience, Monash University, Alfred Hospital, Melbourne, VIC, Australia.
J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):408-11. doi: 10.1136/jnnp.2008.159459. Epub 2008 Nov 7.
The spinocerebellar ataxias (SCAs) are clinically and genetically heterogeneous. Currently, 27 forms are known, with the causative gene identified in 16. Although the majority of dominant pedigrees worldwide have SCAs 1, 2, 3, 6 or 8, new SCAs continue to be delineated. We describe a new disorder: SCA 30.
An Australian family of Anglo-Celtic ethnicity manifested a relatively pure, slowly evolving ataxia. Six affected and four unaffected members were personally examined in a standardised fashion. MRI and nerve conduction studies were performed in two. An autosomal genome-wide linkage study was undertaken, and an in silico analysis of potential candidate genes in the linkage region was performed.
The six affected members had a relatively pure, slowly evolving ataxia developing in mid to late life, with only minor pyramidal signs and no evidence of neuropathy. All had hypermetric saccades with normal vestibulo-ocular reflex gain. Only one displayed (slight) gaze-evoked nystagmus. MRI showed cerebellar atrophy with preservation of nodulus/uvula and brainstem. Linkage analysis excluded currently known SCAs and identified a logarithm (base 10) of odds score of 3.0 at chromosome 4q34.3-q35.1, distinct from all previously reported loci. In silico prioritisation identified the gene ODZ3 as the most likely contender.
SCA 30 is a previously undescribed cause of (relatively) pure adult-onset autosomal dominant cerebellar ataxia. The responsible gene is yet to be determined, but ODZ3 is a plausible candidate.
脊髓小脑共济失调（SCA）在临床和遗传方面具有异质性。目前已知有27种类型，其中16种已确定致病基因。尽管全球大多数显性谱系患有SCA 1、2、3、6或8型，但新的SCA类型仍在不断被发现。我们描述了一种新的疾病：SCA 30型。
一个英裔凯尔特族裔的澳大利亚家庭表现出相对单纯、进展缓慢的共济失调。对6名患者和4名未患病成员进行了标准化的个人检查。对其中2人进行了MRI和神经传导研究。进行了常染色体全基因组连锁研究，并对连锁区域潜在的候选基因进行了电子分析。
6名患者患有相对单纯、进展缓慢的共济失调，发病于中年后期，仅有轻微锥体束征，无神经病变证据。所有人的扫视运动过度，前庭眼反射增益正常。只有1人出现（轻微）凝视诱发性眼球震颤。MRI显示小脑萎缩，小结节/蚓垂和脑干保留。连锁分析排除了目前已知的SCA类型，并在4号染色体q34.3 - q35.1区域确定了对数（以10为底）优势评分3.0，与所有先前报道的位点不同。电子分析确定ODZ3基因为最有可能的候选基因。
SCA 30型是一种此前未被描述的（相对）单纯的成人发病常染色体显性小脑共济失调病因。致病基因尚未确定，但ODZ3基因是一个合理的候选基因。
