Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia
Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia
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DOI：
10.1212/wnl.0000000000004311
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发表时间：
2017-09-05
期刊：
影响因子：
9.9
通讯作者：
Klockgether, Thomas
中科院分区：
文献类型：
--
作者：
Giordano, Ilaria;Harmuth, Florian;Klockgether, Thomas
目的：明确散发性成人起病的退行性共济失调的临床表型和自然病史，并确定可能的致病突变。方法：疾病严重程度的主要衡量标准是共济失调评定量表(SARA)。使用高覆盖率的共济失调特异性基因小组结合下一代测序对DNA样本进行突变筛查。结果：对249名参与者进行了分析。其中，83例在基线时符合临床可能的多系统萎缩小脑型(MSA-C)的诊断标准，另有12例在随访中符合诊断标准。MSA-C标准阳性(4.94+/-0.74，p10岁为散发性成人发病的原因不明/非MSA(SAOA/非MSA))。与MSA-C相比，SAOA/非MSA患者SARA评分较低(13.6+/-6.0vs16.0+/-5.8，p=0.0200)，年SARA增长较慢(1.1vs3.3+/-3.2vs3.3+/-3.2vs3.3+/-3.2p=0.0013)。在194名受试者中，有11人(6%)做出了明确或可能的基因诊断。结论：我们的研究为散发性共济失调的临床表型和进展提供了定量数据。用基因面板方法筛查致病突变，在6%的队列中得到了基因诊断。
Objective: To define the clinical phenotype and natural history of sporadic adult-onset degenerative ataxia and to identify putative disease-causing mutations.Methods: The primary measure of disease severity was the Scale for the Assessment and Rating of Ataxia (SARA). DNA samples were screened for mutations using a high-coverage ataxia-specific gene panel in combination with next-generation sequencing.Results: The analysis was performed on 249 participants. Among them, 83 met diagnostic criteria of clinically probable multiple system atrophy cerebellar type (MSA-C) at baseline and another 12 during follow-up. Positive MSA-C criteria (4.94+/-0.74, p10 years were designated sporadic adult-onset ataxia of unknown etiology/non-MSA (SAOA/non-MSA). Compared with MSA-C, SAOA/non-MSA patients had lower SARA scores (13.6+/-6.0 vs 16.0+/-5.8, p=0.0200) and a slower annual SARA increase (1.1+/-2.3 vs 3.3+/-3.2, p=0.0013). In 11 of 194 tested participants (6%), a definitive or probable genetic diagnosis was made.Conclusions: Our study provides quantitative data on the clinical phenotype and progression of sporadic ataxia with adult onset. Screening for causative mutations with a gene panel approach yielded a genetic diagnosis in 6% of the cohort.