Table 2.
Individuals with rolandic epilepsy (RE) and potentially pathogenic CNVs
| Case ID (gender) | Cytoband | CNV coordinates (hg19/B37) | Size (kb) | CNV type (inheritance) | UCSC gene content | Case phenotype | Family phenotype | Disease association/function |
| 7007-301 (F) | 1p31.1 | chr1:71414151–71469541 | 55 | Del (Mat) | PTGER3 | RE onset 10 years | Paternal half-sister; absences, ADHD, SD, RDG | FS. Inflammation pathway gene. |
| RK029 (M) | 1q22 | chr1:155492432–155644686 | 152 | Dup | ASH1L, ASH1L-AS1, MSTO2P, MSTO1, YY1AP1 | RE onset 5 years, RD, ADHD | Unknown | ASH1L disruptive variants cause ASD, ID, seizures. |
| 1053-301 (M) | 2p12 | chr2:79342216–79461716 | 119 | Dup (de novo) | REG1A, REG1P, REG3A, CTNNA2 | RE onset 6 years, frequent seizures | Father; RD, depression, sister; RD, migraine | CTNNA2; cell–cell adhesion, axon guidance, dendrite aborisation. ADHD, SCZ. |
| S218 (F) | 2q34 | chr2:212410753–212698130 | 287 | Dup | ERBB4 | RE onset 9 years | Cousin; FS, mother; migraine | Early myoclonic encephalopathy. Regulates neuronal excitability and plasticity. |
| 7037-301 (F) | 4p15.2 | chr4:21542615–21566331 | 23 | Del (de novo) | KCNIP4 | RE onset 4 years, RD, ADHD | Mother; RD, migraine | KCNIP4; regulates neuronal excitability. ADHD candidate. |
| S52 (F) | 4q22.1–22.2 | chr4:93556411–94663992 | 1107 | Dup | GRID2 | RE onset 10 years, RD, dyscalculia | Cousin; RE | Glutamate receptor delta2. Causes cerebellar ataxia, DD, SD. |
| 1029-301 (F) | 5q11.2 | chr5:56740642–58265912 | 1525 | Dup (Mat) | ACTBL2, PLK2, GAPT, RAB3C, PDE4D | RE onset 6 years | None | PDE4D functions in memory. PLK2 regulates dendritic spine morphology, increases post seizure. |
| 7007-301 (F) | 8q13.2 | chr8:67998878–68249106 | 250 | Dup (Mat) | CSPP1, ARFGEF1 | RE onset 10 years | Paternal half-sister; absences, ADHD, SD, RDG | ARFGEF1 regulates neurite outgrowth and polarity. EE candidate. |
| SSM (M) | 10q21.3 | chr10:67609352–67731403 | 122 | Del | CTNNA3 | RE onset 8 years, freq seizures, multiple Rx, ADHD, LD. | None | Del in EE and ASD. Cell adhesion molecule, stab. dendritic spines. |
| S38 (M) | 10q23.1 | chr10:83538813–83667589 | 128 | Dup | NRG3 | RE onset 7 years | None | SCZ, bipolar disorder, DD, ASD. Pleiotropic neurodevelopment roles. |
| 1041-301 (M) | 11q14.1 | chr11:84078744–84347934 | 269 | Dup (Mat) | DLG2 | RE onset 9 years | Pat grandmother; migraine, mat grandmother; depression | Assoc. ASD, DD, bipolar disorder. Encodes PSD-93—binds and controls glutamate receptors. |
| 7021-302 (F) | 12q14.3 | chr12:67060969–67382547 | 321 | Del (Mat) | GRIP1 | RE onset 6 years, RD, SD, motor dyspraxia | Mother; ADHD, depression, MIG, sister and brother; MIG, brother RE | Synaptic scaffold protein stabilises glutamate receptors. Increased in epileptic mice. ASD. |
| 1027-301 (M) | 15q21.3 | chr15:54857821–54924743 | 66 | Del (Mat) | UNC13C | RE onset 6 years, RD, SD, ADHD, motor dyspraxia | Maternal aunt and grandfather; LD | Presynaptic protein mediates synaptic vesicle priming and plasticity. |
| SMJ (F) | 15q22.33 | chr15:67426523–67454644 | 28 | Del | SMAD3 | RE onset 10 years, headache | Cousin; grand mal seizures | Pathway regulates synaptogenesis and contributes to seizures in TLE rats. |
| 7034-301 (M) | 17q12 | chr17:31958395–32931677 | 973 | Dup (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) | 20q12 | chr20:41049613–41275309 | 225 | Del | PTPRT | RE onset 4 years, freq seizures, ESES, multiple Rx | Father; FS, mother; ADHD | Regulates synaptic function and neuronal development. |
| 1027-301 (M) | Xq27.3 | chrX:144853754–145033725 | 179 | Del (Mat) | SLITRK2, TMEM257 | RE onset 6 years, RD, SD, ADHD, motor dyspraxia | Maternal 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.