Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy

Table 3 SCN1A mutations in the cohort

Subject	R622	R74	R710	R769
Age	28y	51y	24y	3y
Sex	F	F	F	F
Clinical features	Moderate ID, challenging behaviour	Mild-mod ID, depression	Moderate ID, ataxia, stroke-like episodes	Mod-severe DD, poor coordination
Seizure onset	6 m	3 m	6 m	5d
Syndrome	GGE-ID	FE	PME	CSWS
Seizure types	IS, GTCS, M	FS, FE, EBCS	C-CSE, M, FDS, EBCS	T, GTCS, CSE, FE, At, Abs, M
Genomic coordinates	Chr2 g.166915177 _166915180dup	Chr2 g.166915162 G > A	Chr2 g.166913001 G > C	Chr2 g.166848780 C > T
cDNA	c.283_286dup	c.301C > T	c.393C > G	c.5005G > A
Protein	p.Gly96Glufs*24	p.Arg101Trp	p.Ser131Arg	p.Ala1669Thr
Inheritance	De novo	De novo	Segregates with phenotype	De novo
PhyloP	-	0.91 (highly conserved)	0.89 (highly conserved)	0.86 (highly conserved)
Grantham distance	-	101 (moderate)	110 (moderate)	58 (small)
SIFT	-	0 (deleterious)	0.02 (deleterious)	0 (deleterious)
PolyPhen-2 (HumVar)	-	0.982 (probably damaging)	0.368 (benign)	1 (probably damaging)
CADD (PHRED-scaled)	-	34 (top 0.1 %)	22.3 (top 1 %)	26.1 (top 1 %)
ExAC frequency	0	0	0	0
dbSNP	-	rs121917965	-	-

Age (at recruitment) and seizure onset in y(ears), m(onths) or d(ays). Clinical features: ID intellectual disability, DD developmental delay
Syndrome, electroclinical syndrome or main epilepsy type at recruitment: CSWS, epilepsy with continuous spikes and waves during sleep; FE focal epilepsy, GGE-ID genetic generalised epilepsy with ID, PME progressive myoclonic epilepsy
Seizure types: Abs absence, At atonic, C clonic, 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, T tonic, seizure type at presentation is underlined. Coordinates are based on hg19/GRCh37. Nucleotide and protein reference sequences were NM_001165963.1 and NP_001159435.1

ISSN: 1471-2350