Criscuolo C, Chessa L, Di Giandomenico S, Mancini P, Saccà F, Grieco G S, Piane M, Barbieri F, De Michele G, Banfi S, Pierelli F, Rizzuto N, Santorelli F M, Gallosti L, Filla A, Casali C
Department of Neurological Sciences, Federico II University, Naples, Italy.
Neurology. 2006 Apr 25;66(8):1207-10. doi: 10.1212/01.wnl.0000208402.10512.4a.
Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETX have been described in AOA2 patients.
To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families.
The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations.
All the patients had cerebellar features, including limb and truncal ataxia, and slurred speech. OMA was observed in two patients, extrapyramidal symptoms in two, and mental impairment in three. High serum AFP levels, motor and sensory axonal neuropathy, and marked cerebellar atrophy on MRI were detected in all the patients who underwent these examinations. Sural nerve biopsy revealed a severe depletion of large myelinated fibers in one patient, and both large and small myelinated fibers in another. Postmortem findings are also reported in one of the patients. Four different homozygous SETX mutations were found (a large-scale deletion, a missense change, a single-base deletion, and a splice-site mutation).
The clinical phenotype of oculomotor apraxia type 2 is fairly homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant finding. The identification of new mutations expands the array of SETX variants, and the finding of a missense change outside the helicase domain suggests the existence of at least one more functional region in the N-terminus of senataxin.
2型动眼神经失用性共济失调（AOA2）的特征为发病年龄在10至22岁之间，伴有小脑萎缩、周围神经病变、动眼神经失用（OMA）以及血清甲胎蛋白（AFP）水平升高。已在AOA2患者中发现SETX基因的隐性突变。
描述AOA2的临床特征，并鉴定来自四个意大利家庭的10例患者中的SETX突变。
对患者进行临床检查、常规实验室检测、神经传导研究、腓肠神经活检及脑部MRI检查。对所有患者进行SETX突变筛查。
所有患者均有小脑相关表现，包括肢体和躯干共济失调以及言语不清。两名患者出现OMA，两名出现锥体外系症状，三名出现智力损害。所有接受相关检查的患者均检测到高血清AFP水平、运动和感觉轴索性神经病变以及MRI显示明显的小脑萎缩。腓肠神经活检显示，一名患者大的有髓纤维严重缺失，另一名患者大、小有髓纤维均缺失。还报告了其中一名患者的尸检结果。发现了四种不同的纯合SETX突变（一个大规模缺失、一个错义改变、一个单碱基缺失和一个剪接位点突变）。
2型动眼神经失用的临床表型相当一致，仅显示出轻微的家族内变异性。OMA并非恒定表现。新突变的鉴定扩展了SETX变异体的范围，并且在解旋酶结构域外发现错义改变提示senataxin的N端至少还存在一个功能区域。
