• Test Code:
    1095
  • Department:
  • Test Synonyms:
    ACTBACTG1AHI1ARFGEF2ARL13BARXASPMATRATRXC5ORF42CASKCC2D2ACDK5RAP2CDKL5CDONCENPJCEP152CEP290CEP41COL4A1CUL4BDCXDHCR7DISP1DLL1EMX2EOMESEXOSC3 EZH2FGF8FKRPFKTNFLNAFOXG1FOXH1GAS1GLI2GLI3GPR56HESX1IER3IP1KIAA1279KIF7L1CAMLAMC3LARGEMCPH1MECP2MED12MKS1MRPS16MYCNNFIX NIPBLNODALNPHP1NSD1OFD1OPHN1OTX2PAFAH1B1PCNTPHF6PIK3CAPOMGNT1POMT1POMT2PQBP1PTCH1PTENRAB18RAB3GAP1RAB3GAP2RARS2RBBP8RELNRPGRIP1LSHHSIX3SLC25A19SLC9A6 SOX2SRPX2STILTCF4TCTN1TCTN2TGIF1TMEM138TMEM216TMEM237TMEM67TSEN2TSEN34TSEN54TTC21BTUBA1ATUBA8TUBB2BTUBB3UBE3AUPF3BVLDLRVRK1WDR62ZEB2ZIC2
  • CPT Code(s):
    81408
Background:

Disorders causing brain malformations are phenotypically heterogeneous; mutations in certain genes have been associated inherited conditions causing brain developmental issues. These conditions could present with dysmorphologic features including holoprosencephaly, microcephaly and macrocephaly. Other clinical phenotypes include dysmorphologies observed in MRIs, seizures, developmental delays and intellectual disability. These conditions could include lissencephalies, cerebellar hypoplasia, Joubert syndrome and Joubert-like disorders. Conditions causing brain malformations can be inherited in an autosomal dominant, recessive and X-linked pattern.

Reasons for Referral:

  • Suspected genetic etiology of a brain malformation
  • Carrier testing
  • Positive family history

Methodology:

Next generation sequencing will analyze the exons or coding regions of 107 Comprehensive Brain Malformation-associated genes using Illumina NextSeq 500 technology.  Samples are prepared using hybridization probes to enrich exonic regions.  Promoter, intronic, etc. regions are not assessed on our assay, but may contain variants that impact gene function. Additionally, the assay does not assess coding regions with incompletely coverage including regions of high homology (pseudogenes), regions of high GC content and polynucleotide repeats, etc.

Coding region coverage for the Comprehensive Brain Malformations panel genes

Gene Name

Coverage

ACTB, ACTG1, AHI1, ARFGEF2, ARL13B, ASPM, ATR, ATRX, CASK, CC2D2A, CDK5RAP2, CDKL5, CDON, CENPJ, CEP152, CEP290, CEP41, COL4A1, CUL4B, DCX, DHCR7, DISP1, DLL1, EMX2, EXOSC3, EZH2, FGF8, FKTN, FLNA, GLI3, GPR56, HESX1, IER3IP1, L1CAM, LAMC3, LARGE, MCPH1, MECP2, MED12, MKS1, MRPS16, NFIX, NIPBL, NODAL, NPHP1, NSD1, OFD1, OPHN1, OTX2, PAFAH1B1, PCNT, PHF6, PIK3CA, POMGNT1, POMT1, POMT2, PQBP1, PTCH1, PTEN, RAB18, RAB3GAP1, RAB3GAP2, RARS2, RBBP8, RELN, RPGRIP1L, SLC25A19, SLC9A6, SOX2, SRPX2, STIL, TCF4, TCTN1, TCTN2, TGIF1, TMEM138, TMEM216, TMEM237, TMEM67, TSEN2, TTC21B, TUBA1A, TUBA8, TUBB3, UBE3A, UPF3B, VLDLR, VRK1, WDR62, ZEB2

95%-100%

C5orf42, EOMES, KIAA1279, KIF7,TSEN34, TSEN54

90%-95%

FKRP, FOXG1, FOXH1, GLI2, MYCN, SHH, SIX3, TUBB2B

75%-90%

ARX*, GAS1, ZIC2

50%-75%

Coding regions below 95% may be covered upon request if further assessment of a gene is necessary (some exceptions may apply). Please contact Knight Diagnostic Laboratories for more information.
*ARX gene complete coverage and expansions in the polyalanine tract not available.

Related Tests: Knight Diagnostic Laboratories offers smaller, focused panels:

Specimen Requirements:

  • Blood:  EDTA or ACD (Solution A or B):
  • Adult: 5 mL
  • Child: 5 mL
  • Infant: 2-3 mL
  • Saliva: 1 ORAgene Saliva Kit (OGR-500)
  • Skin Fibroblast: Punch Biopsy, or 2 T-25 confluent flasks
  • DNA: 1-2µg at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

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A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

8 weeks

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided.
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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