Comprehensive Epilepsy and Autism Panel (401)
Related Genes: ABAT, ABCD1, ACSL4, ACY1, ADGRG1, ADGRV1, ADNP, ADSL, AFF2, AGO1, AHI1, AIFM1, ALDH5A1, ALDH7A1, ALG13, AMT, ANK3, ANKRD11, AP1S2, AP4B1, AP4E1, AP4M1, AP4S1, ARFGEF2, ARHGEF9, ARID1A, ARID1B, ARX, ASPM, ATP13A2, ATP1A2, ATP2A2, ATP6AP2, ATP6V0A2, ATP7A, ATP8A2, ATR, ATRX, AUTS2, BCKDK, BCL11A, BCOR, BRAF, BRWD3, C12ORF57, CA8, CACNA1A, CACNA1C, CACNA1H, CACNA2D2, CACNB4, CASK, CASR, CBL, CC2D1A, CCDC22, CCDC88C, CCM2, CDKL5, CDKN1C, CHD2, CHD7, CHD8, CHRNA2, CHRNA4, CHRNA7, CHRNB2, CLCN2, CLCN4, CLN3, CLN5, CLN6, CLN8, CNTNAP2, COL18A1, COL4A1, CPA6, CREBBP, CSTB, CTCF, CTNNB1, CTSD, CUL3, CUL4B, CYP27A1, D2HGDH, DCX, DDHD2, DDX3X, DEAF1, DEPDC5, DHCR7, DIS3L2, DKC1, DLG3, DMD, DNAJC5, DNM1, DNMT3A, DOCK7, DPYD, DYNC1H1, DYRK1A, EBP, EEF1A2, EFHC1, EHMT1, EIF2S3, ELP4, EMX2, EPM2A, EZH2, FGD1, FGFR3, FKRP, FLNA, FLVCR2, FMR1, FOLR1, FOXG1, FOXP1, FOXP2, FTSJ1, GABRA1, GABRB2, GABRB3, GABRD, GABRG2, GAMT, GATAD2B, GATM, GCSH, GDI1, GK, GLDC, GLI2, GLI3, GNAO1, GNB1, GNS, GOSR2, GPC3, GPHN, GRIA3, GRIK2, GRIN1, GRIN2A, GRIN2B, GRIP1, HCCS, HCN1, HCN4, HDAC8, HGSNAT, HIP1, HNRNPU, HPRT1, HRAS, HSD17B10, HTRA1, HUWE1, IDS, IL1RAPL1, IQSEC2, ITPA, KANSL1, KAT6A, KAT6B, KCNA1, KCNA2, KCNB1, KCNJ1, KCNJ10, KCNJ11, KCNMA1, KCNQ2, KCNQ3, KCNT1, KCTD13, KCTD7, KDM5C, KDM6A, KIF1A, KIF1BP, KIRREL3, KMT2A, KMT2D, KRAS, KRIT1, L1CAM, L2HGDH, LAMC3, LAMP2, LARGE1, LAS1L, LBR, LGI1, LIAS, LINS1, LRP2, MAGEL2, MAGI2, MAN1B1, MAOA, MAP2K1, MAP2K2, MAPK10, MBD5, MBTPS2, MCPH1, MECP2, MED12, MED13L, MED23, MEF2C, MFSD8, MID1, MTHFR, MTOR, MYT1L, NAA10, NAGLU, NDE1, NDP, NDUFA1, NECAP1, NEXMIF, NF1, NFIX, NHLRC1, NHS, NIPBL, NLGN4X, NOTCH3, NPRL2, NPRL3, NRAS, NRXN1, NRXN3, NSD1, NSDHL, NSUN2, OCRL, OFD1, OPHN1, OTC, PACS1, PAFAH1B1, PAK3, PANK2, PAX6, PCDH19, PDCD10, PDHA1, PGK1, PHF6, PHF8, PIGA, PIGN, PIGO, PIGV, PLA2G6, PLCB1, PLP1, PNKP, PNPO, POGZ, POLG, POMGNT1, POMT1, POMT2, PORCN, PPT1, PQBP1, PRICKLE1, PRICKLE2, PRPS1, PRRT2, PTCH1, PTCHD1, PTEN, PTPN11, PURA, RAB39B, RAD21, RAF1, RAI1, RARS2, RBM10, RELN, RIT1, RNASEH2A, RNASEH2B, RNASEH2C, ROGDI, RPL10, RPS6KA3, SAMHD1, SATB2, SCARB2, SCN1A, SCN1B, SCN2A, SCN3A, SCN5A, SCN8A, SCN9A, SERPINI1, SETBP1, SETD2, SETD5, SGSH, SHANK2, SHANK3, SHOC2, SIK1, SLC12A5, SLC13A5, SLC16A2, SLC19A3, SLC1A2, SLC25A1, SLC25A19, SLC25A22, SLC2A1, SLC35A2, SLC4A10, SLC6A1, SLC6A4, SLC6A8, SLC9A6, SMARCA2, SMARCA4, SMARCB1, SMARCE1, SMC1A, SMC3, SMS, SNAP25, SNAP29, SOS1, SOX11, SOX5, SPRED1, SPTAN1, ST3GAL3, ST3GAL5, STX1B, STXBP1, SYN1, SYNGAP1, SYP, SZT2, TAF1, TBC1D24, TBL1XR1, TBR1, TBX1, TCF12, TCF20, TCF4, THOC2, TIMM8A, TMEM231, TMLHE, TPP1, TRAPPC9, TREX1, TRIO, TRPM6, TSC1, TSC2, TSPAN7, TUBA1A, TUBA8, TUBB, TUBB2A, TUBB2B, TUBB3, TUBG1, TUSC3, UBE2A, UBE3A, UNC80, UPF3B, USP9X, VANGL1, VPS13A, VPS13B, WAC, WDR45, WDR62, WDR81, WWOX, YWHAE, ZC4H2, ZDHHC9, ZEB2, ZMYND11, ZNF407, ZNF711
Autism spectrum disorders are a group of complex disorders of brain development characterized by difficulties in social interaction, verbal and nonverbal communication, and a restricted set of activities and/or interests. By most recent estimates, ASD effects approximately 1 in 59 children and is four times more likely to be diagnosed in boys than girls. Signs begin early in childhood, with developmental delays in social interaction and language present before 3 years of age, and the associated challenges last throughout a person’s life. In some cases, autism is part of a more complex genetic syndrome with other characteristics, although it can also be isolated.
Epilepsy is a neurological condition that is characterized by recurrent, unprovoked seizures that affects approximately 1.2% of the population in the US. While epilepsy can develop due to a physical insult to the brain, there are also many genetic forms of epilepsy. It is a spectrum condition with a wide range of seizure types and age of onset, varying from person-to-person. Individuals with epilepsy may also develop other neurological problems as a result of recurrent seizures. It is estimated that up to 10% of individuals with epilepsy also have ASD, with a higher prevalence in males and in syndromic cases.
The Comprehensive Epilepsy and Autism Panel includes 401 genes, encompassing all genes in the following subpanels: Comprehensive Autism Spectrum Disorder Panel (228 genes) and the Comprehensive Epilepsy Panel (226 genes). The included genes are associated with syndromic and non-syndromic causes of autism spectrum disorders (ASD), intellectual disability, and epilepsy. Given the clinical overlap between these disorders, comprehensive testing allows time- and cost-effective evaluations of multiple conditions. The disorders included in this panel may be inherited in an autosomal dominant (AD), autosomal recessive (AR), or X-linked (XL) manner.
Some of the genes in this panel are not fully penetrant, meaning that an individual may have a genetic with a pathogenic variant but not display any of the signs/symptoms of the disorder. Additionally, these disorders may have variable expressivity indicating that individuals carrying the same pathogenic variant may display differing cellular and clinical features and/or differing severity.
Clinical Utility: Genetic testing of an individual may be indicated to distinguish hereditary disorders from acquired (non-genetic) causes, provide information on the likelihood of related health issues, guide clinical management, and establish disease risk to other family members and future generations.
Methods: The Comprehensive Epilepsy and Autism Panel and subpanels offered by Sema4 primarily utilize next-generation sequencing (NGS) to identify variants within the genes analyzed. Copy number variant (CNV) detection by NGS is also utilized to increase diagnostic yield. Supplemental and confirmatory technology used in this panel may include targeted genotyping, multiplex ligation-dependent probe amplification (MLPA), exon array, quantitative PCR, and Sanger sequencing. For Fragile X, PCR is performed along with capillary electrophoresis for allele sizing. Samples positive for FMR1 CGG repeats in the premutation and full mutation size range have additional analysis via Southern blot to assess the size and methylation status. Ultra high-resolution medical exon array (UHRMEA) is available for deletion/duplication studies of gene(s) within this panel as either reflex (add-on), concurrent, or standalone test. UHRMEA provides single exon level coverage for the majority of the exons within this panel. Variant classification and interpretation are performed based on the American College of Medical Genetics Standards and guidelines for the interpretation of sequence variants.
A high-resolution chromosomal microarray (HRP) is available as an additional test, which is to identify DNA copy number variants (CNVs) associated with chromosome imbalances including gains and losses throughout the genome, as well as absence of heterozygosity (AOH) that can be indicative of uniparental disomy (UPD) or regions of the genome identical by descent (IBD).
Targeted Testing: Targeted familial mutation analysis or single gene testing is available for any of the genes on this panel. Prenatal diagnosis is also available for known familial variants; please contact our laboratory at 800-298-6470 to discuss prior to sending any prenatal samples.
Postnatal blood samples:
2 yellow-top (ACD-A or ACD-B) or 2 lavender-top (EDTA) tubes, 5-10 mL of blood from the patient are required. One blood tube from both parents is requested.
1 yellow-top (ACD-A or ACD-B) or 1 lavender-top (EDTA) tube, 2 mL of blood from the patient are required. Additionally, 1 yellow-top (ACD-A or ACD-B) or 1 lavender-top (EDTA) 5-10 mL tube of blood from both parents is requested.
Please inquire with lab (800-298-6470 option 2)
Prenatal testing for a known familial variant:
- Two confluent T-25 flasks of cultured cells from amniotic fluid or chorionic villi
- >4 mg of direct chorionic villi tissue
- 15 mL of direct amniotic fluid
- 5-10 mL of blood in an EDTA tube (lavender top) is required from each biological parent. Parental blood samples may be used for maternal cell contamination studies or confirmation studies.
- Send in previous report of known familial variant with specimen
- A minimum of 10 μL DNA (50-250 ng/μL) is required for testing. 20 μL DNA (50-350 ng/μL) is recommended
- Saliva specimens are accepted upon request. Please contact our laboratory to obtain saliva kits
- Saliva samples should be collected in Oragene DNA (OG-500) kits by DNA Genotek
- 1 cheek swab specimen collected from ORAGENE kit from the patient is required. 1 cheek swab specimen collected from ORAGENE kit from both parents is requested.
Samples should be kept and shipped refrigerated or at room temperature. Do not freeze specimens.
Include the following with each sample:
- Completed and signed test requisition form and informed consent
- Billing information or payment (include copy of insurance card)
- Contact information for referring physician
- Testing to be performed
- Indication for testing, patient’s family history, ethnic background and prior relevant test results
Send same day or overnight (check for morning delivery) to:
62 Southfield Ave
Stamford, CT 06902
Results are reported in 3-4 weeks (for postnatal samples) from the receipt of the specimen.
- Comprehensive Autism Spectrum Disorder Panel (228)
- Comprehensive Epilepsy Panel (226)
- STAT Autism Spectrum Disorder Subpanel (30)
- Syndromic Epilepsy and Intellectual Disability Subpanel (93)
- Chromosome Microarray (aCGH 180K +SNP)