Test Code: 1394

Autism Spectrum Disorders: Gene Panel
Test Code: 1394
Turnaround time: 6 weeks

CONDITION DESCRIPTION

Genetics of Autism Spectrum Disorders
Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders which include autism, pervasive developmental delay-not otherwise specified (PDD-NOS), and Asperger syndrome. ASDs are characterized by impairments in social relationships, variable degrees of language and communication deficits, and repetitive behaviors and/or a narrow range of interests. The age of onset is prior to age 3 with a variable clinical presentation, ranging in severity both amongst individuals as well as amongst the various subtypes of ASDs. Additional clinical features may also be observed in individuals with an ASD, such as intellectual disability (up to ~50%) and seizures (~25%).

Known genetic causes of autism include cytogenetically visible chromosome abnormalities (3-5%), copy number variants – which include submicroscopic deletions and duplications (~6-7%), and single gene disorders (~5%).

*Please note that some genes on this panel are associated with additional phenotypes. All components of the Autism Panel can be ordered separately.

References:

  • Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006 Principal Investigators and the CDC (2009).
  • MMWR Surveill Summ, 58:1-20.
  • Bolton et al. (2011). Br J Psychiatry, 198:289-294.
  • Vorstman et al. (2006) Mol Psych, 11:18-28.
  • Shen et al. (2010). Pediatrics, 125:e727-35.
  • Miles JH (2011). Genet Med, 13:278-94.
  • Schaefer et al. (2008). Genet Med, 10:301-5.

GENES

ADSL, AFF2, ALDH5A1, AP1S2, ARX, ATRX, BCKDK, BRAF, CACNA1C, CASK, CDKL5, CHD7, CHD8, CNTNAP2, CREBBP, CYP27A1, DHCR7, DMD, EHMT1, FGD1, FMR1, FOLR1, FOXG1, FOXP1, FOXP2, HPRT1, KDM5C, L1CAM, MAGEL2, MBD5, MECP2, MED12, MEF2C, MID1, NHS, NIPBL, NLGN3, NLGN4X, NR1I3, NRXN1, NSD1, OPHN1, PAFAH1B1, PCDH19, PHF6, PNKP, PQBP1, PTCHD1, PTEN, PTPN11, RAB39B, RAI1, RELN, SCN1A, SLC2A1, SLC9A6, SMARCB1, SMC1A, TCF4, UBE2A, UBE3A, VPS13B, ZEB2

INDICATIONS
This test is indicated for:

  • Confirmation of a clinical diagnosis of autism or an autism spectrum disorder.
  • Carrier testing in adults with a family history of autism or an autism spectrum disorder.

METHODOLOGY

Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient’s genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not mean to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient’s gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

FRAXE: Alleles in the normal and premutation range are detected by PCR amplification and fragment analysis. Males: Methylation sensitive PCR is performed to determine AFF2/FMR2 methylation status. Females: Southern blot analysis is performed to detect expanded alleles of the FMR2 gene.

DETECTION

Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.
Analytical Sensitivity: ~99%.

FRAXE: All cases of FRAXE syndrome caused by CCG expansion of the AFF2/FMR2 gene will be detected by this assay. Rare cases of FRAXE syndrome caused by mutation of the AFF2/FMR2 gene will not be detected by this assay.

REFERENCE RANGE
Next Generation Sequencing: NA

FRAXE: Normal: Approximately 6-35 CCG repeats. Affected: Approximately >200 CCG repeats and methylation of expanded allele.

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types

Type: Whole Blood
Specimen Requirements: In EDTA (purple top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.

Type: Isolated DNA
Specimen Requirements: In microtainer: 60 μg
Isolation using the QiagenTM Puregene kit for DNA extraction is recommended.

Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.

RELATED TESTS

  • Autism Spectrum Disorders: Deletion/Duplication Analysis