Table 3.
Pathogenic variants in known epileptic encephalopathy genes
| Gene | Proband (Gender) |
Inheritance (inference) | cDNA change | Protein change | Diagnosis |
|---|---|---|---|---|---|
| SCN1A | T23445(F) | De novo (P) | c.4836delC | Ile1613Phefs*5 | Dravet |
| T1639(M) | Segregates (P) | c.5962G>A | Arg1988Trp | Epilepsy-Aphasia, FS + | |
| T18466 (M) | De novo (P) | c.4033G>A | Pro1345Ser | EOEE | |
| T18594 (M) | Segregates (P) % | c.133C>T | Asp45Asn | Epilepsy-Aphasia, FS + | |
| T19875 (F) | De novo (P) | c.3977G>A | Ala1326Val | Epilepsy-Aphasia | |
| T18775 (M) | Segregates (P) % | c.1076T>G | Asn359Thr | Dravet (ICEGTC) 29 | |
| T18997 (M) | Unk, parents unavailable (LP) | c.1209delA | Phe403Leufs*12 | Dravet | |
| T19963 (M) | De novo (P) | c.4453T>C | Asn1485Asp | Dravet | |
| SCN2A | T20632 (M) | De novo (P) | c.408G>T | Met136Ile | EOEE evolving to IS |
| T21005 (F) | De novo (P) | c.2715G>C | Lys905Asn | EE | |
| T22816(F) | Unk, father unavailable (LP) | c.2783T>G | Phe928Cys# | EE | |
| T20340 (F) | De novo (P) | c.1154delC | Ile1021Tyrfs*16 | LGS | |
| T24127 (F) | De novo (P) | c.5645G>A | Arg1882Gln | EE | |
| PCDH19 | T23579 (F) | X-linked, female restricted (P) | c.1681G>A | Pro561Ser | EE |
| T23305 (F) | X-linked, female restricted (P) | c.2873C>T | Arg958Gln | LGS | |
| CDKL5 | T20819 (M) | De novo (P) | c.464-2A>G | Unk | EOEE |
| T22724 (M) | Inherited from unaffected mother, X-linked (P) | c.433C>T | His145Tyr | EE | |
| T22954 (F) | De novo (P) | c.545T>C | Leu182Pro | EOEE | |
| T897(F) | De novo (P) | c.2564C>G | Ser855* | IS | |
| T23057 (M) | De novo (P) | c.1926delT | Leu642Argfs*16 | IS | |
| T23951 (M) | De novo (P) | c.533G>A | Arg178Gln | EOEE | |
| T23234 (F) | De novo (P) | c.620G>A | Gly207Glu | EE | |
| T24139 (M) | Unk, parents unavailable (LP) | c.1926delT | Leu642Argfs*16 | EOEE | |
| STXBP1 | T22595 (M) | De novo (P) | c.1154delC | Met387Tyrfs*17 | Ohtahara |
| T1266 (M) | Unk, mother unavailable (LP) | c.1630G>T | Gly544Cys# | LGS | |
| T23151 (F) | De novo (P) | c.125C>T | Ser42Phe | EOEE | |
| T23553 (F) | De novo (P) | c.238T>C | Ser80Pro | EE | |
| T23122 (M) | De novo (P) | c.568C>T | Arg190Trp | EOEE | |
| T22856 (M) | De novo (P) | c.1060T>C | Cys354Arg | Ohtahara | |
| T23289 (M) | De novo (P) | c.1708G>A | Thr570Ala | EE | |
| UBE3A | T23859 (F) | Inherited from unaffected mother, affected sib also mutation positive (P) | c.1585G>A | Arg506Cys& | EE – features suggestive of Angelman syndrome |
| SCN8A | T3929 (M) | Inherited from somatic mosaic father @ (P) | c.3868C>G | Leu1290Val | EE |
| KCNQ2 | T24158 (M) | De novo (P) | c.587G>A | Ala196Val | EOEE |
| T23919 (F) | De novo (P) | c.602C>T | Arg201His | EOEE/IS | |
| PNPO | T23451 (M) | Homozygous recessive (P) | c.686G>A | Arg229Gln^ | EME |
| PNKP | T23141 (M) | Homozygous recessive (P) | c.58G>A | Pro20Ser | EE |
M- male F-female; P – pathogenic, LP – likely pathogenic;
variant segregates with the disorder, pedigrees Supplementary Figure 5;
Two missense variants likely pathogenic (see methods);
known pathogenic variant 30,
father is somatic mosaic, with 13% of cells carrying alternate, pathogenic allele;
known pathogenic variant dbSNP:rs104894629 31.
Accession numbers: SCN1A, NM_001165963.1, NP_001159435.1; SCN2A, NM_021007.2, NP_066287.2; PCDH19, NM_001184880.1, NP_001171809.1; CDKL5, NM_001037343.1, NP_001032420.1; STXBP1, NP_003165.3, NM_ 001032221.3; UBE3A, NM_000462.3, NP_000453.2; SCN8A, NM_001177984.2; NP_001171455.1; KCNQ2, NM_004518.4, NP_004509.2; PNPO, NM018129.3, NP_060599.1;PNKP, NM_007254.3, NP009185.2
EE = epileptic encephalopathy not otherwise specified: EOEE = early onset epileptic encephalopathy; EME = early myoclonic encephalopathy; FS + = febrile seizures plus; ICEGTC = intractable childhood epilepsy with generalized tonic clonic seizures; LGS = Lennox Gastaut syndrome; IS = Infantile spasms, Unk = unknown