Table 1.
Trio | CNV | Size | Candidate or Known Epilepsy Genes or Known Disease Association | De Novo SNV Calls from Exome2 | Validation Platform | Gene(s) Enriched in CNVs Found in Patients with Neurodevelopmental Phenotypesa | Age at Onset | Seizure Typesb |
---|---|---|---|---|---|---|---|---|
Likely pathogenic CNVs | ||||||||
fx | 2q24 dup | 7.5Mb | SCN2A, SCN1A | SMG9 (mis), EPHB1 (synon) | CGH | SCN1A, SCN2A | 7 mo | IS |
iq | 2q24 del | 296kb | SCN1A | None | CGH, SNP | SCN1A | <1 yr | GTC, aA |
hj | 5p15 del | 3.8Mb | SEMA5A, CTNND2 | SDCBP2 (mis) | CGH | TAS2R1, FAM173B, CCT5, MTRR | 6 mo | FS, focal, GTC, aA, SE |
cy | 7q11 del | 11.4Mb | MAGI2, YWHAG, HIP1 | ZNF12 (UTR), FPGT‐TNNI3K (mis), FAM50A | CGH, SNP | HIP1 | 3 mo | IS, aA |
aia | 9p ter del | 8.7Mb | 9p deletion syndrome | None | SNP | DMRT2, DMRT3 | 5 mo | IS |
iz | 14q23 del | 585kb | GPHN | HRG (mis), PCDHB13 (mis) | CGH | —c | 2.5 yr | FS+SE, T, drop |
eh | 15q11 dup | 5.0Mb | 15q11q13 dup syndrome; GABRB3 | PAQR8 (synon) | CGH | GABRB3 | 2 wk | IS, multiple other |
ag | 15q11 dupd | 12.0Mb | 15q11q13 dup syndrome; GABRB3 | MLL4 (mis) | CGH, karyo | GABRB3 | 8 mo | IS |
gq∧ | 15q11 dup | 8.4Mb | 15q11q13 dup syndrome; GABRB3 | None | CGH, SNP | GABRB3 | 8 mo | GTC, T, atonic |
fu | t(15;16)d | 1.8Mb del, 16.3Mb dup | Large unbalanced translocation | None | CGH, karyo | SNRPA1, FANCA | 8 mo | IS |
CNVs of uncertain clinical significance | ||||||||
ig | 1p22 dup | 140kb | 1 gene: ZNF644 | IQSEC1 (mis) | CGH, SNP | —c | 2 yr | A, GTC, M, T, drop |
ad | 1q21 dup | 249kb | TAR region dup | NFE2L1 (mis) | SNP | LIX1L | 8 mo | IS |
aib | 2q37 del | 154kb | 4 genes: PPP1R7, HDLBP, ANO7, SEPT2 | CXXC11 (synon) | SNP | PPP1R7 | 5 mo | IS, T |
gc | 7q22 del | 622kb | 15 genes in region | NR1H2 (mis) | CGH | MUC17, MYL10, TRIM56 | 8 mo | IS |
ahp | 7q31 dup | 94kb | 2 genes: CPED1, ING3 | ADAMSL4 (mis), PPP6R2 (mis) | SNP | —c | 7 mo | IS |
le | 8p23 del | 140kb | 2 genes: MCPH1, AGTP2 | DACH2 (mis) | CGH, SNP | ANGPT2 | 3 y 10 mo | GTC, drop, T, M, A, aA |
bda | 17q12 del | 1.5Mb | 15 genes in region | None | h.c. | 8 mo | IS, M, SE, GTC |
Additional information is available in Supplementary Table 7.
Genes listed represent those with mean probability value < 0.05 for known disease gene(s) in region or peak probability value < 0.05 for novel regions as described by Cooper and colleagues.21 See Supplementary Table 5 for details.
Seizure types include all reported; first type listed was the initial seizure type.
No gene within region with p < 0.05.
Upon review of records, diagnosis made prior to enrollment.
A = absence; aA = atypical absence; CGH = comparative genome hybridization; CNV = copy number variant; FS = febrile seizures; GTC = generalized tonic clonic; h.c. = high‐confidence CNV call by CoNIFER; IS = infantile spasms; M = myoclonic; SE = status epilepticus; SNP = single nucleotide polymorphism; SNV = single nucleotide variant; T = tonic; UTR = untranslated region.