Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2:: a clinical and genetic study in 18 patients
Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2:: a clinical and genetic study in 18 patients
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DOI：
10.1093/brain/awh080
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发表时间：
2004-04-01
期刊：
影响因子：
14.5
通讯作者：
Dürr, A
中科院分区：
文献类型：
--
作者：
Le Ber, I;Bouslam, N;Dürr, A
共济失调伴动眼运动性失用2型(AOA2)是一种新发现的常染色体隐性遗传性小脑共济失调(ARCA)，由3个共有步态共济失调、动眼运动性失用和/或甲胎蛋白(AFP)水平升高的家系的9q34基因定位所致。我们评估了77个进行性非Friedreich ARCA家系，并确定了6个AOA2表型提示的家系。6个家系均确认连锁，D9S1830的最高Lod评分为5.91。我们报告了第一个详细的表型研究，包括神经心理学、眼科和脑成像检查，这是迄今为止招募的最大系列的AOA2患者。平均发病年龄为15.1±3.8岁。感觉运动神经病(92%)和编舞或肌张力障碍运动(44%)常见。在56%的患者中观察到动眼失用症，其特征是水平眼跳潜伏期延长和子宫下层。AFP水平在100%的家系中升高，使其成为有用的生物标志物。本研究首次发现AOA2可在欧洲、北非和西印度群岛发现，其相对频率与非Friedreich ARCA的8%相似，在我们的成人患者系列中，AOA2的相对频率高于共济失调毛细血管扩张症和共济失调伴动眼运动性失用1型(AOA1)。因此，在成人中，AOA2可能是迄今为止发现的最常见的ARCA原因，仅次于Friedreich‘s共济失调。
Ataxia with oculomotor apraxia type 2 (AOA2) is a newly described autosomal recessive cerebellar ataxia (ARCA) defined by genetic location to 9q34 of three families sharing gait ataxia, oculomotor apraxia and/or elevated alpha-foetoprotein (AFP) levels. We have evaluated 77 families with progressive non-Friedreich ARCA and have identified six families with a phenotype suggestive of AOA2. Linkage was confirmed in all six families, with a maximal lod score of 5.91 at D9S1830. We report the first detailed phenotypic study, including neuropsychological, oculographic and brain imaging investigations, in the largest series of AOA2 patients yet recruited. The mean age at onset was 15.1 +/- 3.8 years. Sensory motor neuropathy (92%) and choreic or dystonic movements (44%) were frequent. Oculomotor apraxia was observed in 56% of patients and characterized by increased horizontal saccade latencies and hypometria. AFP levels were elevated in 100% of the families, making it a useful biological marker. This study shows for the first time that AOA2 can be found in Europe, North Africa and the West Indies, and its relative frequency represents similar to8% of non-Friedreich ARCA, which is more frequent than ataxia telangiectasia and ataxia with oculomotor apraxia type 1 (AOA1), in our series of adult patients. In adults, AOA2 may be, therefore, the most frequent cause of ARCA identified so far, after Friedreich's ataxia.