Table 2

Individuals with rolandic epilepsy (RE) and potentially pathogenic CNVs

Case ID (gender)CytobandCNV coordinates (hg19/B37)Size (kb)CNV type (inheritance)UCSC gene contentCase phenotypeFamily phenotypeDisease association/function
7007-301 (F)1p31.1chr1:71414151–7146954155Del (Mat) PTGER3 RE onset 10 yearsPaternal half-sister; absences, ADHD, SD, RDGFS. Inflammation pathway gene.
RK029 (M)1q22chr1:155492432–155644686152Dup ASH1L, ASH1L-AS1, MSTO2P, MSTO1, YY1AP1 RE onset 5 years, RD, ADHDUnknown ASH1L disruptive variants cause ASD, ID, seizures.
1053-301 (M)2p12chr2:79342216–79461716119Dup (de novo) REG1A, REG1P, REG3A, CTNNA2 RE onset 6 years, frequent seizuresFather; RD, depression, sister; RD, migraineCTNNA2; cell–cell adhesion, axon guidance, dendrite aborisation. ADHD, SCZ.
S218 (F)2q34chr2:212410753–212698130287Dup ERBB4 RE onset 9 yearsCousin; FS, mother; migraineEarly myoclonic encephalopathy. Regulates neuronal excitability and plasticity.
7037-301 (F)4p15.2chr4:21542615–2156633123Del (de novo) KCNIP4 RE onset 4 years, RD, ADHDMother; RD, migraine KCNIP4; regulates neuronal excitability. ADHD candidate.
S52 (F)4q22.1–22.2chr4:93556411–946639921107Dup GRID2 RE onset 10 years, RD, dyscalculiaCousin; REGlutamate receptor delta2. Causes cerebellar ataxia, DD, SD.
1029-301 (F)5q11.2chr5:56740642–582659121525Dup (Mat) ACTBL2, PLK2, GAPT, RAB3C, PDE4D RE onset 6 yearsNone PDE4D functions in memory. PLK2 regulates dendritic spine morphology, increases post seizure.
7007-301 (F)8q13.2chr8:67998878–68249106250Dup (Mat) CSPP1, ARFGEF1 RE onset 10 yearsPaternal half-sister; absences, ADHD, SD, RDG ARFGEF1 regulates neurite outgrowth and polarity. EE candidate.
SSM (M)10q21.3chr10:67609352–67731403122Del CTNNA3 RE onset 8 years, freq seizures, multiple Rx, ADHD, LD.NoneDel in EE and ASD. Cell adhesion molecule, stab. dendritic spines.
S38 (M)10q23.1chr10:83538813–83667589128Dup NRG3 RE onset 7 yearsNoneSCZ, bipolar disorder, DD, ASD. Pleiotropic neurodevelopment roles.
1041-301 (M)11q14.1chr11:84078744–84347934269Dup (Mat) DLG2 RE onset 9 yearsPat grandmother; migraine, mat grandmother; depressionAssoc. ASD, DD, bipolar disorder. Encodes PSD-93—binds and controls glutamate receptors.
7021-302 (F)12q14.3chr12:67060969–67382547321Del (Mat) GRIP1 RE onset 6 years, RD, SD, motor dyspraxiaMother; ADHD, depression, MIG, sister and brother; MIG, brother RESynaptic scaffold protein stabilises glutamate receptors. Increased in epileptic mice. ASD.
1027-301 (M)15q21.3chr15:54857821–5492474366Del (Mat) UNC13C RE onset 6 years, RD, SD, ADHD, motor dyspraxiaMaternal aunt and grandfather; LDPresynaptic protein mediates synaptic vesicle priming and plasticity.
SMJ (F)15q22.33chr15:67426523–6745464428Del SMAD3 RE onset 10 years, headacheCousin; grand mal seizuresPathway regulates synaptogenesis and contributes to seizures in TLE rats.
7034-301 (M)17q12chr17:31958395–32931677973Dup (Mat) ASIC2, CCL2, CCL7, CCL11, CCL8, CCL13, CCL1, C17orf102, TMEM132E RE onset 5 years, frequent seizures, multiple Rx, SD, RD.Mother; FS, migraine; mat uncle and aunt; RD, migraine, FS, mat cousin; RD ASIC2; ion channel, activity terminates seizures.
NVH (M)20q12chr20:41049613–41275309225Del PTPRT RE onset 4 years, freq seizures, ESES, multiple RxFather; FS, mother; ADHDRegulates synaptic function and neuronal development.
1027-301 (M)Xq27.3chrX:144853754–145033725179Del (Mat) SLITRK2, TMEM257 RE onset 6 years, RD, SD, ADHD, motor dyspraxiaMaternal aunt and grandfather; LD SLITRK2: assoc. SCZ, ASD, RD. Controls excitatory synapse formation.
  • Genetic and clinical characteristics of 15 patients with RE and their families who carried CNVs classed as potentially pathogenic. Two patients, 7007-301 and 1027-301, carried two potentially pathogenic CNVs. S218 and SMJ also carry a pathogenic CNV, table 1.

  • References can be found in online supplementary table S3.

  • ASD, autism spectrum disorder; DD, developmental delay; F, female; FH, family history; FS, febrile seizures; ID, intellectual disability; LD, learning difficulties; LI, language impairment; M, male; Mat, maternal; MIG, migraine; Pat, paternal ; RD; reading difficulty or dyslexia;  SCZ, schizophrenia; SD, speech disorder; UCSC, University of California, Santa Cruz.