Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.
Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.
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DOI：
10.1371/journal.pgen.1000962
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发表时间：
2010-05-20
期刊：
影响因子：
4.5
通讯作者：
Eichler EE
中科院分区：
文献类型：
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作者：
Mefford HC;Muhle H;Ostertag P;von Spiczak S;Buysse K;Baker C;Franke A;Malafosse A;Genton P;Thomas P;Gurnett CA;Schreiber S;Bassuk AG;Guipponi M;Stephani U;Helbig I;Eichler EE
癫痫是人类最常见的神经系统疾病之一，患病率为 1%，终生发病率为 3%。已在罕见的常染色体显性和严重散发性癫痫中发现了一些基因，但绝大多数病例的遗传原因尚不清楚。已知拷贝数变异 (CNV) 在许多神经发育障碍的遗传病因学中发挥重要作用，包括智力障碍 (ID)、自闭症和精神分裂症。尚未进行癫痫拷贝数变异的全基因组研究。我们对 517 名患有各种特发性非病变性癫痫的个体进行了全基因组寡核苷酸阵列比较基因组杂交。我们在 8.9% 的受影响个体中检测到一种或多种罕见基因 CNV，而这些在 2,493 名对照个体中不存在；五个人有两个罕见的 CNV。我们在先前与其他神经发育障碍有关的基因中发现了 CNV，包括 AUTS2 中的两个缺失和 CNTNAP2 中的一个缺失。因此，我们的研究结果表明，罕见的 CNV 可能导致广泛的全身性和局灶性癫痫。此外，我们发现 2.9% 的患者在 15q11.2、15q13.3 或 16p13.11 处携带缺失，这些基因组热点先前与智力障碍、自闭症或精神分裂症相关。总之，我们的研究结果表明了智力障碍、自闭症、精神分裂症和癫痫等看似不同的疾病的共同病因。癫痫是一种常见的神经系统疾病，其特征是反复发作，影响高达 3% 的人口。在某些情况下，癫痫有明确的病因，例如大脑异常或头部受伤。然而，在许多情况下，没有明显的原因。大量研究表明，遗传因素在这些类型的癫痫中很重要，但尽管已知几种癫痫基因，但我们仍然只能在极少数病例中确定遗传原因。为了识别导致癫痫遗传原因的新基因，我们在人类基因组中搜索了约 500 名癫痫患者中未发现的基因缺失（缺失拷贝）和重复（额外拷贝）。使用这种方法，我们发现了几个大的缺失，这些缺失对于至少 3% 的癫痫病例很重要。此外，我们还发现了新的候选基因，其中一些也被认为在其他相关疾病（如自闭症和智力障碍）中发挥着作用。这些基因是癫痫患者进一步研究的候选基因。
Epilepsy is one of the most common neurological disorders in humans with a prevalence of 1% and a lifetime incidence of 3%. Several genes have been identified in rare autosomal dominant and severe sporadic forms of epilepsy, but the genetic cause is unknown in the vast majority of cases. Copy number variants (CNVs) are known to play an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID), autism, and schizophrenia. Genome-wide studies of copy number variation in epilepsy have not been performed. We have applied whole-genome oligonucleotide array comparative genomic hybridization to a cohort of 517 individuals with various idiopathic, non-lesional epilepsies. We detected one or more rare genic CNVs in 8.9% of affected individuals that are not present in 2,493 controls; five individuals had two rare CNVs. We identified CNVs in genes previously implicated in other neurodevelopmental disorders, including two deletions in AUTS2 and one deletion in CNTNAP2. Therefore, our findings indicate that rare CNVs are likely to contribute to a broad range of generalized and focal epilepsies. In addition, we find that 2.9% of patients carry deletions at 15q11.2, 15q13.3, or 16p13.11, genomic hotspots previously associated with ID, autism, or schizophrenia. In summary, our findings suggest common etiological factors for seemingly diverse diseases such as ID, autism, schizophrenia, and epilepsy. Epilepsy, a common neurological disorder characterized by recurrent seizures, affects up to 3% of the population. In some cases, the epilepsy has a clear cause such as an abnormality in the brain or a head injury. However, in many cases there is no obvious cause. Numerous studies have shown that genetic factors are important in these types of epilepsy, but although several epilepsy genes are known, we can still only identify the genetic cause in a very small fraction of cases. In order to identify new genes that contribute to the genetic causes of epilepsy, we searched the human genome for deletions (missing copies) and duplications (extra copies) of genes in ∼500 patients with epilepsy that are not found in control individuals. Using this approach, we identified several large deletions that are important in at least 3% of epilepsy cases. Furthermore, we found new candidate genes, some of which are also thought to play a role in other related disorders such as autism and intellectual disability. These genes are candidates for further studies in patients with epilepsy.
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影响因子：
4
作者：
Ben-Shachar S;Lanpher B;German JR;Qasaymeh M;Potocki L;Nagamani SC;Franco LM;Malphrus A;Bottenfield GW;Spence JE;Amato S;Rousseau JA;Moghaddam B;Skinner C;Skinner SA;Bernes S;Armstrong N;Shinawi M;Stankiewicz P;Patel A;Cheung SW;Lupski JR;Beaudet AL;Sahoo T
通讯作者：
Sahoo T
影响因子：
3.5
作者：
Dibbens, Leanne M.;Mullen, Saul;Berkovic, Samuel F.
通讯作者：
Berkovic, Samuel F.
影响因子：
9.8
作者：
Friedman, J. M.;Baross, Agnes;Marra, Marco A.
通讯作者：
Marra, Marco A.
影响因子：
56.9
作者：
Bailey, JA;Gu, ZP;Eichler, EE
通讯作者：
Eichler, EE
影响因子：
64.8
作者：
通讯作者：
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