Phenotype and genotype analysis in amyotrophic lateral sclerosis with TARDBP gene mutations
Phenotype and genotype analysis in amyotrophic lateral sclerosis with TARDBP gene mutations
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DOI：
10.1212/wnl.0b013e3182553c88
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发表时间：
2012-05-01
期刊：
影响因子：
9.9
通讯作者：
Camu, W.
中科院分区：
文献类型：
--
作者：
Corcia, P.;Valdmanis, P.;Camu, W.
目的：描述的表型和表型-基因型相关性与肌萎缩侧索硬化症（ALS）患者的TARDBP基因mutations.Methods：法国TARDBP+ ALS患者（n = 28）进行了比较，首先到3个队列：737散发性ALS（SALS），192非突变的家族性ALS（FALS），和58 SOD 1 + FALS，然后到117 TARDBP+例文献。最常见的TARDBP突变的基因型-表型相关性进行了研究。结果：在TARDBP+患者中，发病较早（p = 0.0003），上肢（UL）发病占主导地位（p = 0.002），持续时间较长（p = 0.0001）比SALS患者。TARDBP+和SOD 1+组持续时间最长，但发病部位不同：TARDBP+组64.3% UL发病，SOD 1+组74.1%下肢发病（p < 0.0001）。我们的28例患者的临床特征与文献中的117例相似。在高加索人中，51.3%的人有UL发作，而58.8%的亚洲人有延髓发作（p = 0.02）。突变类型影响生存率（p < 0.0001），而位于TARDBP超富甘氨酸残基结构域的G298 S1与最差生存率（27个月）相关。结论：各组表型的差异以及TARBDP突变对生存率的不同影响可能有助于医生在ALS管理中的应用，并允许改进遗传诊断策略。神经病学（R）2012;78：1519-1526
Objective: To describe the phenotype and phenotype-genotype correlations in patients with amyotrophic lateral sclerosis (ALS) with TARDBP gene mutations.Methods: French TARDBP+ patients with ALS (n = 28) were compared first to 3 cohorts: 737 sporadic ALS (SALS), 192 nonmutated familial ALS (FALS), and 58 SOD1 + FALS, and then to 117 TARDBP+ cases from the literature. Genotype-phenotype correlations were studied for the most frequent TARDBP mutations.Results: In TARDBP+ patients, onset was earlier (p = 0.0003), upper limb (UL) onset was predominant (p = 0.002), and duration was longer (p = 0.0001) than in patients with SALS. TARDBP+ and SOD1+ groups had the longest duration but diverged for site of onset: 64.3% UL onset for TARDBP+ and 74.1% on lower limbs for SOD1+ (p < 0.0001). The clinical characteristics of our 28 patients were similar to the 117 cases from the literature. In Caucasians, 51.3% of had UL onset, while 58.8% of Asians had bulbar onset (p = 0.02). The type of mutation influenced survival (p < 0.0001), and the G298S1, lying in the TARDBP super rich glycine-residue domain, was associated with the worst survival (27 months).Conclusion: Differences in phenotype between the groups as well as the differential influence of TARBDP mutations on survival may help physicians in ALS management and allow refining the strategy of genetic diagnosis. Neurology (R) 2012;78:1519-1526