Table 2.
Rare CNVs detected in 80 patients with ID/DD and epilepsy
| Subject | Age | Sex | Clinical features | Seizure onset | Syndrome | Seizure types | Cytoband | CNV Type | Coordinates | Size (Kb) | Tests | Status | Interpretation | Genes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R125 | 10 m | F | Severe DD, cleft palate | 3 m | EIMFS | FE, EBCS, CSE | 2q24.3 | Del | 163823021–167958723 | 4,136 | c/f | DN | Path | SCN3A, SCN2A, SCN1A, SCN9A, SCN7A & 8 others |
| R351 | 15y | M | Moderate DD, poor coordination, joint contractures, mildly dysmorphic | 3 m | Dravet | FS, GTCS, CSE, M | 2q24.3 | Del | 166842637–166918932 | 76 | c/d | DN | Path | SCN1A |
| R404 | 7y | F | Mild DD, ASD | 8 m | West | IS, Abs | 16p11.2 | Del | 29595483–30198151 | 603 | b/e,f | DN | Path | DOC2A, KIF22, MAPK3, PRRT2, QPRT, SEZ6L2 & 24 others |
| R660 | 21y | M | Mod-severe ID, challenging behaviour, ASD, depression, dysmorphic | 8 m | GGE-ID | Abs, M, FDS, EBCS | 9q34.3 | Del | 140707889–140890373 | 182 | b/e | DN | Path | CACNA1B, EHMT1 |
| 3p14.2 | Dup | 59736299–61023355 | 1,287 | b/e | Pat | Likely | FHIT | |||||||
| 3p22.1 | Del | 41359533–41824555 | 465 | b/e | Mat | VUS | ULK4 | |||||||
| R911 | 22y | F | Mod ID, small head, mildly dysmorphic | 10y | FE | FDS, GTCS | 2q22.3 | Del | 148691873–148818437 | 127 | b/e | DN | Path | MBD5, ORC4 |
| R913 | 20y | M | Mod-severe ID, challenging behaviour, ASD | 10 m | FE | FS, FDS, EBCS | 16p13.11 | Dup | 15512574–16262571 | 750 | b/e | Mat | Likely | ABCC1, C16orf45, FOPNL, KIAA0430, MIR484, MYH11, NDE1 |
| R345 | 27y | F | Mild ID, dysmorphic | <6y | GGE-ID | M, Abs, GTCS | 2q13 | Del | 111392259–113094793 | 1,703 | b/e | Pat | Likely | BUB1, BCL2L11, ANAPC1, MERTK, FBLN7 & 5 others |
| R58 | 26y | F | Severe ID, scoliosis | <8y | GGE-ID | At, Abs, M | 1q21.1 | Dup | 145625979–145723645 | 98 | a/e | Mat | VUS | CD160, RNF115 |
| R74a | 51y | F | Mild-mod ID, depression | 3 m | FE | FS, FE, EBCS | 1p21.1 | Del | 104167778–104297867 | 130 | a/e | U | VUS | AMY1A, AMY1B, AMY1C, AMY2A |
| R101 | 32y | M | ID, seizures | <16y | U | U | 11q22.3 | Del | 109173027–109325299 | 152 | b/e | Pat | VUS | C11orf87 |
| R198 | 19y | M | Severe ID, ASD, mild right hemiparesis | 7 m | LGS | FE, IS, Abs, NCS, GTCS, At, FDS | Xq28 | Del | 150589930–150811921 | 222 | c/nd | U | VUS | PASD1 |
| R528 | 23y | M | Severe ID, challenging behaviour, ASD, dysmorphic, regression | 11y | FE | FE, Abs | 15q13.3 | Dup | 32019919–32514341 | 494 | b/e | U | VUS | CHRNA7 |
| R605 | 41y | M | ID, seizures | <16y | U | U | 15q11.2 | Dup | 22383292–23272733 | 889 | b/e | Pat | VUS | CYFIP1, NIPA1, NIPA2, TUBGCP5 & 8 others |
| 8p23.1 | Del | 11713852–12204679 | 491 | b/e | Mat | VUS | CTSB, FAM66D, FAM86B1, USP17L2, ZNF705D & 6 others | |||||||
| R622a | 28y | F | Moderate ID, challenging behaviour | 6 m | GGE-ID | IS, GTCS, M | 18p11.22 | Dup | 10042023–10581304 | 539 | b/e | Mat | VUS | APCDD1, NAPG |
| R650 | 21y | M | Mild ID, thin habitus, depression | 18 m | GGE-ID | Abs, M, GTCS | 15q13.3 | Dup | 32029693–32514926 | 485 | a/nd | U | VUS | CHRNA7 |
| 15q14 | Del | 34700297–34807869 | 108 | a/nd | U | VUS | GOLGA8A | |||||||
| R786 | 9y | M | Moderate DD, Leg hypertonia, dystonia | 2y | GGE-ID (M) | M, Abs, At | 21q21.3 | Del | 27715263–27955385 | 240 | a/e | Mat | VUS | CYYR1 |
| R931 | 15y | F | Severe DD, ASD, dysmorphic, microcephaly | 12y | GGE-ID | GTCS | 7q11.22 | Del | 71815170–72305671 | 491 | b/e | Pat | VUS | CALN1, MIR4650-1, MIR4650-2, SBDSP1, TYW1B |
| R981 | 5y | F | Severe DD, regression, ASD, leg hypertonia | 1w | GGE-ID | Abs, At, M, T | 3p26.3 | Dup | 726675-1301830 | 575 | c/nd | U | VUS | CNTN6 |
Age (at recruitment) and seizure onset in y(ears), m(onths) or w(eeks). Clinical features: ID intellectual disability, DD, developmental delay, ASD autism spectrum disorder
Syndrome, electroclinical syndrome or main epilepsy type at recruitment: Dravet, Dravet syndrome; EIMFS, epilepsy of infancy with migrating focal seizures: FE focal epilepsy, GGE-ID, genetic generalised epilepsy with ID, LGS Lennox-Gastaut syndrome, U unknown, West West syndrome
Seizure types: Abs absence, At atonic, CSE convulsive status epilepticus, EBCS evolution to bilateral or convulsive seizures, FDS focal dyscognitive seizures, FS febrile seizures, GTCS generalised tonic-clonic seizures, IS infantile spasms, M myoclonic, NCS non-convulsive status epilepticus, T tonic, seizure type at presentation is underlined (when known)
CNV type, Dup(lication) or Del(eletion). Coordinates, chromosome position of first/last abnormal probes based on hg19/GRCh37. Tests, primary array/confirmation method: (a) Illumina610-Quad SNP-array, (b) Illumina OmniExpress SNP-array, (c) BlueGnome CytoChip array CGH, (d) quantitative PCR, (e) Illumina Exome BeadChip or custom Illumina SNP array, (f) fluorescence in situ hybridization, and (nd) not done. Status: DN, de novo; inherited Pat(ernally); Mat(ernally) or U(nknown). Interpretation (of clinical significance): Path(ogenic); Likely, likely pathogenic; VUS, variant of uncertain significance
aPatients R622 and R74 had pathogenic SCN1A mutations which suggests these two CNVs are likely to be benign