Department of Genetics, Lyon University Hospital, Lyon, France; Claude Bernard Lyon I University, Lyon, France; CRNL, CNRS UMR 5292, INSERM U1028, Lyon, France.
Epilepsia. 2014 Feb;55(2):370-8. doi: 10.1111/epi.12502. Epub 2013 Dec 24.
Rolandic epilepsies (REs) represent the most frequent epilepsy in childhood. Patients may experience cognitive, speech, language, reading, and behavioral issues. The genetic origin of REs has long been debated. The participation of rare copy number variations (CNVs) in the pathophysiology of various human epilepsies has been increasingly recognized. However, no systematic search for microdeletions or microduplications has been reported in RE so far.
Array comparative genomic hybridization (aCGH) and quantitative polymerase chain reaction (qPCR) were used to analyze the genomic status of a series of 47 unrelated RE patients who displayed various types of electroclinical manifestations.
Thirty rare CNVs were detected in 21 RE patients. Two CNVs were de novo, 12 were inherited, and 16 were of unknown inheritance. Each CNV was unique to one given patient, except for a 16p11.2 duplication found in two patients. The CNVs of highest interest comprised or disrupted strong candidate or confirmed genes for epileptic and other neurodevelopmental disorders, including BRWD3, GRIN2A, KCNC3, PRKCE, PRRT2, SHANK1, and TSPAN7.
Patients with REs showed rare microdeletions and microduplications with high frequency and heterogeneity. Whereas only a subset of all genomic alterations found here may actually participate in the phenotype, the novel de novo events as well as several inherited CNVs contain or disrupt genes, some of which are likely to influence the emergence, the presentation, or the comorbidity of RE. The future screening of cohorts of larger size will help in detecting more de novo or recurrent events and in appreciating the possible enrichment of specific CNVs in patients with RE.
Rolandic 癫痫（RE）是儿童期最常见的癫痫类型。患者可能会出现认知、言语、语言、阅读和行为问题。RE 的遗传起源由来已久。越来越多的人认识到，罕见的拷贝数变异（CNVs）参与了各种人类癫痫的病理生理学。然而，迄今为止，尚未有报道系统地寻找 RE 中的微缺失或微重复。
使用阵列比较基因组杂交（aCGH）和定量聚合酶链反应（qPCR）分析了 47 名无关联的 RE 患者的基因组状态，这些患者表现出各种类型的电临床症状。
在 21 名 RE 患者中检测到 30 个罕见的 CNV。2 个 CNV 是新生的，12 个是遗传的，16 个是未知遗传的。每个 CNV 仅存在于一个特定的患者中，除了在两个患者中发现的 16p11.2 重复。最受关注的 CNV 包括或破坏了癫痫和其他神经发育障碍的强候选或已确认基因，包括 BRWD3、GRIN2A、KCNC3、PRKCE、PRRT2、SHANK1 和 TSPAN7。
RE 患者表现出罕见的微缺失和微重复，频率高且异质性大。虽然这里发现的所有基因组改变中只有一部分可能实际参与表型，但新的新生事件和几个遗传的 CNV 包含或破坏了一些可能影响 RE 出现、表现或合并症的基因。未来对更大规模队列的筛查将有助于检测更多的新生或复发性事件，并评估特定 CNV 在 RE 患者中的可能富集。
