Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia.
Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia.
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DOI：
10.1001/jamaneurol.2014.1944
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发表时间：
2014-10
期刊：
影响因子：
29
通讯作者：
Nelson, Stanley F.
中科院分区：
文献类型：
--
作者：
Fogel, Brent L.;Lee, Hane;Deignan, Joshua L.;Strom, Samuel P.;Kantarci, Sibel;Wang, Xizhe;Quintero-Rivera, Fabiola;Vilain, Eric;Grody, Wayne W.;Perlman, Susan;Geschwind, Daniel H.;Nelson, Stanley F.
小脑共济失调是一种神经系统疾病的不同集合，其原因从常见的后天病因到罕见的遗传条件。许多遗传性疾病与慢性进行性共济失调相关，因此这对临床医生提出了关于如何在具有这种临床异质性表型的患者中进行基因检测并优先进行基因检测的诊断挑战。此外，虽然基因检测在早发性和/或家族性病例中的价值似乎是明确的，但许多共济失调患者偶尔出现成人症状，遗传变异对这些患者表型的贡献尚未确定。研究遗传性疾病在成人型和散发型小脑性共济失调患者中的作用。我们连续研究了76例到三级转诊中心评估慢性进行性小脑共济失调的患者。下一代外显子组测序结合全面的生物信息学分析、表型分析和临床相关性。我们在超过60%的研究患者（n = 46）中确定了临床相关的遗传信息，包括21%（n = 16）的诊断性致病基因变异，考虑到小脑共济失调的遗传学多样性和临床异质性，这是一个显著的结果。这项研究表明，在成人发作和散发性共济失调患者中进行临床外显子组测序是一种高产率测试，在超过五分之一的患者中提供了明确的诊断，并在超过三分之一的患者中提出了潜在的诊断，以指导额外的表型和诊断评估。因此，临床外显子组测序是一个适当的考虑，在常规遗传评估的所有患者表现为慢性进行性小脑共济失调。
Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1093/brain/awt315
发表时间：
2014-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Foley AR;Menezes MP;Pandraud A;Gonzalez MA;Al-Odaib A;Abrams AJ;Sugano K;Yonezawa A;Manzur AY;Burns J;Hughes I;McCullagh BG;Jungbluth H;Lim MJ;Lin JP;Megarbane A;Urtizberea JA;Shah AH;Antony J;Webster R;Broomfield A;Ng J;Mathew AA;O'Byrne JJ;Forman E;Scoto M;Prasad M;O'Brien K;Olpin S;Oppenheim M;Hargreaves I;Land JM;Wang MX;Carpenter K;Horvath R;Straub V;Lek M;Gold W;Farrell MO;Brandner S;Phadke R;Matsubara K;McGarvey ML;Scherer SS;Baxter PS;King MD;Clayton P;Rahman S;Reilly MM;Ouvrier RA;Christodoulou J;Züchner S;Muntoni F;Houlden H
通讯作者：
Houlden H
影响因子：
1.4
作者：
Fogel, Brent L.;Vickrey, Barbara G.;Browner, Carole H.
通讯作者：
Browner, Carole H.
影响因子：
7
作者：
Ng, PC;Henikoff, S
通讯作者：
Henikoff, S
影响因子：
14.5
作者：
Johnson, Janel O.;Gibbs, J. Raphael;Singleton, Andrew B.
通讯作者：
Singleton, Andrew B.