A subset of genomic alterations detected in rolandic epilepsies contains candidate or known epilepsy genes including GRIN2A and PRRT2

作者：Dimassi Sarra; Labalme Audrey; Lesca Gaetan; Rudolf Gabrielle; Bruneau Nadine; Hirsch Edouard; Arzimanoglou Alexis; Motte Jacques; Martin Anne de Saint; Boutry Kryza Nadia; Cloarec Robin; Benitto Afaf; Ameil Agnes; Edery Patrick; Ryvlin Philippe; De Bellescize Julitta; Szepetowski Pierre^*; Sanlaville Damien

来源：Epilepsia, 2014, 55(2): 370-378.

DOI：10.1111/epi.12502

• PRRT2
• 16p11.2 duplication
• Rolandic epilepsy
• GRIN2A
• Array-CGH

Objectives 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. Methods 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. Results 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. Significance 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.

• 出版日期2014-2