Severe Infantile Epilepsy 134 Panel Background This panel of 134 is designed to assist in the diagnosis of genetic forms of severe infantile epilepsy. Epileptic encephalopathies are characterized by recurrent intractable seizures and persistent abnormality of cortical function which results in impaired cognitive, sensory and motor development. In the majority of patients, the epilepsy is caused by structural brain malformations, acquired brain insults or inborn errors of metabolism. However, a proportion of cases have a genetic cause. Identification of a causative mutation provides information on prognosis, avoids unnecessary investigations, informs treatment and is useful for genetic counselling.

Genes For a full list of genes included in this panel please see below.

Recommended Clinical Referral Criteria • Patients with epileptic encephalopathy but without an apparent aetiology on the basis of clinical evaluation, normal neuro-imaging and negative results on metabolic screening.

Molecular Analysis

Mutation screen: Next Generation Sequencing (NGS) – target genes are enriched using an Illumina TruSight One assay and sequenced on an Illumina HiSeq . This assay aims to cover the coding sequence and 5bp of flanking intron to a minimum vertical depth of 20X. Where this is not achieved (i.e. % horizontal coverage is less than 100%) due to design or patient-specific gaps then Sanger sequencing is available for some of the genes on request. The selection of gaps to be filled may be guided by the patient’s phenotype or by interaction with the referring clinician Dosage analysis – by MLPA; one reaction is carried out as part of the screen if requested by the referring clinician. Additional analyses can be arranged.

Family follow-up: Testing for known familial mutations in any of the genes in the panel

Prices* & Turnaround Times (TAT) * Valid until March 2019 - prices apply to NHS referrals; non-NHS patients are subject to 20% surcharge Test TAT(working days) Price Severe infantile epilepsy panel screen – includes one MLPA reaction if 80 £750 requested by the referring clinician Additional MLPA analyses 20 £100 Testing for known familial mutations/variants the genes listed above – single £160 20** sample (multiple samples sent together – price per sample) (£90) ** This TAT may be exceeded if primers have to be ordered; if a 20 day TAT is important for your case please give prior notification to the laboratory

Contact Details Sample Requirements Links All Wales Molecular Genetics Laboratory, Blood – 5ml in EDTA (1ml UKGTN - http://ukgtn.nhs.uk/ Institute of Medical Genetics, neonates/infants); Orphanet - http://www.orpha.net/ University Hospital of Wales, Please contact lab prior to sending EDDNAL - http://www.eddnal.com/ Heath Park, a prenatal sample. OMIM - http://www.omim.org/ Cardiff CF14 4XW Please label samples with three Gene Testing Registry - http://www.ncbi.nlm.nih.gov/gtr/ Tel: 029 2074 2641 identifiers and date of collection Fax: 029 2074 4043 All samples must be Support [email protected] accompanied by request form http://www.epilepsy.org.uk/ http://www.wales.nhs.uk/AWMGS/ Consent for testing & DNA storage http://www.cafamily.org.uk/medical- is assumed when request for test information/conditions/w/west-syndrome/ Accredited to ISO 15189:2012 received http://youngepilepsy.org.uk/ (8988 )

Cardiff and Vale University Health Board Date of issue: 26/09/2018 Revision: 5 Filename: MI-GEN-EIEE_NGS

Author: Matthew Howells Authorised by: Michelle Wood Page 1 of 2

Full Gene List

ABAT CLN5 GAMT KCTD7 POLG SMS ADSL CLN6 GATM KIAA1279 PPT1 SPTAN1 ALDH7A1 CLN8 GLRA1 KIAA2022 PRICKLE1 SRPX2 ALG13 CNTNAP2 GLRB LGI1 PRICKLE2 ST3GAL3 ARHGEF9 COL4A1 GLYCTK MAGI2 PRODH STXBP1 ARID1B COL4A2 GOSR2 MAPK10 PRRT2 SUOX ARX CPA6 GPHN MBD5 RANBP2 SYNGAP1 ATP1A2 CRH GPR98 MECP2 RYR3 TBC1D24 ATP1A3 CSTB GRIN1 MEF2C SCARB2 TBL1XR1 ATRX CTSD GRIN2A MFF SCN1A TCF4 BTD DIAPH1 GRIN2B MFSD8 SCN1B TPP1 CACNA1A DNM1 GSS MOCS1 SCN2A TRPM6 CACNA1H DPYD HCN1 MOCS2 SCN2B TSC1 CACNB4 DYRK1A HLCS MOGS SCN8A UBE2A CASK EFHC1 HNRNPU NEDD4L SCN9A UBE3A CASR EHMT1 IDH2 NHLRC1 SLC16A2 WDR45 CBL EPM2A IQSEC2 NRXN1 SLC25A22 WDR45B CDKL5 FOXG1 ITPA PCDH19 SLC2A1 WWOX CHD2 FTL KCNA1 PHF6 SLC6A1 ZEB2 CHRNA2 GABRA1 KCNJ10 PIGA SLC6A19 CHRNA4 GABRB3 KCNMA1 PLCB1 SLC6A5 CHRNB2 GABRD KCNQ2 PNKP SLC6A8 CLN3 GABRG2 KCNQ3 PNPO SLC9A6

Cardiff and Vale University Health Board Date of issue: 26/09/2018 Revision: 5 Filename: MI-GEN-EIEE_NGS

Author: Matthew Howells Authorised by: Michelle Wood Page 2 of 2