Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia
Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia
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DOI：
10.1001/archneur.60.7.982
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发表时间：
2003-07-01
影响因子：
--
通讯作者：
Hentati, F
中科院分区：
文献类型：
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作者：
El Euch-Fayache, G;Lalani, I;Hentati, F
背景资料：Charlevoix-Saguenay的常染色体隐性痉挛性共济失调（ARSACS）是魁北克报道的由SACS基因（染色体13 q12）突变引起的临床同质性疾病。最近，我们确定了一个突尼斯的亲属证明连锁的ARSACS locus.Objective：报告临床，神经生理学和神经活检的结果，患者常染色体隐性小脑共济失调相关的SACS基因在突尼斯。患者和方法：早期乳腺癌患者的遗传连锁分析发病常染色体隐性小脑共济失调允许确定4个家庭，其中18例患者表现出连锁的ARSACS基因座。采用国际共济失调评定量表对患者进行评定。大多数患者进行了周围神经传导、感觉诱发电位和神经活检。结果：平均发病年龄为4.5岁。临床表型定型，并与进行性小脑综合征，锥体综合征与膝反射活跃，巴宾斯基征和踝反射缺失。病人的病程各不相同。感觉诱发电位显示严重的后柱受累。周围神经检查显示轴突和脱髓鞘神经病变。结论：在突尼斯，与SACS基因相关的常染色体隐性遗传性小脑性共济失调表现为同质性表型和异质性等位基因突变。
Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a clinically homogenous disorder reported in Quebec caused by mutations in the SACS gene (chromosome 13q12). Recently, we identified a Tunisian kindred demonstrating linkage to the ARSACS locus.Objective: To report clinical, neurophysiological, and nerve biopsy findings in patients with autosomal recessive cerebellar ataxia related to the SACS gene in Tunisia.Patients and Methods: Genetic linkage analysis of patients with early-onset autosomal recessive cerebellar ataxia allowed the identification of 4 families from which 18 patients demonstrated linkage to the ARSACS locus. The patients were evaluated according to the International Cooperative Ataxia Rating Scale. Peripheral nerve conduction, sensory evoked potentials, and nerve biopsy were performed in most patients.Results: The mean age at onset was 4.5 years. The clinical phenotype was stereotyped and associated with a progressive cerebellar syndrome, a pyramidal syndrome with brisk knee reflexes, and Babinski sign and absent ankle reflexes. The course of the disease varied among patients. Sensory evoked potentials showed severe posterior column involvement. Peripheral nerve investigations demonstrated axonal and demyelinating neuropathy. Four mutations, 2 missense and 2 nonsense, were found.Conclusion: In Tunisia, autosomal recessive cerebellar ataxia related to the SACS gene demonstrated a homogenous phenotype and heterogeneous allelic mutations.