Megalencephaly Panel
General Information
Lab Name
Megalencephaly Panel
Lab Code
MEGPX
Epic Name
Megalencephaly Panel
Description
Megalencephaly Panel is useful for the evaluation of patients with a suspected megalencephaly syndrome. The panel uses next- generation sequencing to detect most mutations in ABCC9, AKT1, AKT2, AKT3, BRAF, BRWD3, CCND2, CDKN1C, CHD8, CRADD, CSF1R, CTNNB1, DEPDC5, DNMT3A, EED, EZH2, FGFR1, FLT4, GATA2, GLI3, GNA11, GNAQ, GNAS, GPC3, HEPACAM, HRAS, IDH1, IDH2, KCNJ8, KRAS, MAP2K1, MED12, MET, MTOR, NPRL2, NPRL3, NRAS, NSD1, PDGFRB, PIK3CA, PIK3R2, PTCH1, PTEN, PTPN11, RASA1, SETD2, SMAD4, STRADA, TSC1, TSC2. The assay completely sequences all exons of these genes AND detects large deletions, duplications and mosaicism.
Genes Tested
| Gene | Disease | Reference (PMID) |
|---|---|---|
| ABCC9 | Cantu syndrome | 22610116 |
| AKT1 | Proteus syndrome | 21793738,22876373 |
| AKT2 | Asymmetric overgrowth with hypoglycemia | 21979934 |
| AKT3 | Hemimegalencephaly, Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, focal cortical dysplasia | 22729224,25722288 |
| BRWD3 | X-linked intellectual disability and macrocephaly | 17668385 |
| CCND2 | Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome | 24705253 |
| CDKN1C | IMAGe syndrome, Beckwith Wiedemann | 20301568,24624461 |
| CHD8 | Intellectual developmental disorder with autism and macrocephaly | 31721432, 31980904 |
| DEPDC5 | Focal epilepsy with or without focal cortical dysplasia, familal focal epilepsy with variable foci | 23542701,23542697 |
| DNMT3A | Tatton-Brown-Rahman Syndrome | 24614070 |
| EED | Overgrowth and macrocephaly | 25787343 |
| EZH2 | Weaver syndrome | 23865096 |
| GLI3 | Greig cephalosyndactyly, Acrocallosal syndrome | 20301619,12414818 |
| GNAQ | Sturge Weber Syndrome, capillary malformation (port-wine) | 23656586 |
| GNAS | Fibrous Dysplasia/McCune-Albright Syndrome, Pseudopseudohypoparathyroidism, pseudohypoparathyroidism 1A, 1B, and progressive osseous heterotopia | 25719192 |
| GPC3 | Simpson-Golabi-Behmel syndrome | 20301398 |
| KCNJ8 | Cantu syndrome | 24700710 |
| MED12 | Opitz-Kaveggia syndrome | 20301719 |
| MTOR | Megalencephaly, hemimegalencephaly, focal cortical dysplasia | 25799227 |
| NPRL2 | Epilepsy, familial focal, with variable foci 2 | 26505888, 27173016 |
| NPRL3 | Epilepsy, familial focal, with variable foci 3 | 26285051 35136953 |
| NSD1 | Sotos syndrome | 20301652 |
| PIK3CA | PIK3CA-related overgrowth syndromes (PROS), Megalencephaly with capillary malformation (MCAP), CLOVES syndrome, megalencephaly, hemimegalencephaly, focal cortical dysplasia, Klippel Trenauney syndrome, isolated lymphatic malformations, isolated venous malformations | 23946963,25681199,22729224,26637981 |
| PTCH1 | Nevoid basal cell carcinoma syndrome, Basal Cell Nevus Syndrome, Gorlin syndrome | 20301330 |
| PTEN | Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome (BRRS) PTEN related hamartoma syndrome, autism, focal cortical dysplasia | 20301661 |
| SETD2 | Overgrowth and macrocephaly | 24852293 |
| TSC1 | Tuberous Sclerosis | 20301399 |
| TSC2 | Tuberous Sclerosis | 20301399 |
For previous versions of MegaPlex™ - Megalencephaly Panel, see Previous Versions, MEGPX.
References
- Pritchard CC, et al. ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J Mol Diagn 2012, 14:357-66. 22658618
- Walsh T, et al. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci U S A 2010, 107:12629-33. 20616022
- Nord AS, Lee M, King MC, and Walsh T. Accurate and exact CNV identification from targeted high-throughput sequence data. BMC Genomics 2011, 12:184. 21486468
- Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet 2010, 11:31-46. 19997069
Synonyms
ABCC9, AKT1, AKT2, AKT3, autism, BRAF, BRWD3, CCND2, CDKN1C, CHD8, Chiari malformation, CRADD, CSF1R, CTNNB1, DEPDC5, developmental delay, DNMT3A, EED, EZH2, FGFR1, FLT4, GATA2, GLI3, GNA11, GNAQ, GNAS, GPC3, hemihypertrophy, HEPACAM, HRAS, hydrocephalus, IDH1, IDH2, KCNJ8, KRAS, macrocephaly, MAP2K1, MED12, Megaplex, MET, MTOR, next-generation sequencing, NPRL2, NPRL3, NRAS, NSD1, overgrowth syndrome, PDGFRB, PIK3CA, PIK3R2, polydactyly, PTCH1, PTEN, PTPN11, RASA1, seizures SETD2, SMAD4, STRADA, syndactyly TSC1, TSC2, tuberous sclerosis, ventriculomegaly
Components
| Code | Name |
|---|---|
| MEGGS | Megalencephaly Genes Analyzed |
| MEGRE | Megalencephaly Panel Result |
| MEGIN | Megalencephaly Panel Interp |
| MEGCH | Megalencephaly Panel Clin Hist |
| MEGMT | Megalencephaly Panel Methods |
| MEGDI | Megalencephaly Lab Director |
Interpretation
Method
Next-generation sequencing.
Sequences are aligned to the human genome reference (hg19). Test performed by targeted capture for listed genes followed by next-generation sequencing with Illumina technology. This test was developed and its performance characteristics were determined by the University of Washington Department of Laboratory Medicine. It has not been cleared or approved by the US Food and Drug Administration. This laboratory is certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high-complexity clinical laboratory testing. This test is used for clinical purposes. It should not be regarded as investigational or for research.
Reference Range
See individual components
Ref. Range Notes
No mutations detected.
Guidelines
Ordering & Collection
Specimen Type
Collection
Preferred:
1. Skin biopsy: 2-4 mm punch biopsy of skin collected under sterile conditions and place in sterile vials with 1-3 mL of transport medium. For specific requirements including preferred transport medium, call cytogenetics laboratory. Do not put biopsy in formaldehyde, formalin, alcohol, 5% dextrose or medium buffered with bicarbonate. Skin biopsies may be routed to cytogenetics for culturing fibroblasts.
For patients within the UW Medicine system: Once biopsy has been obtained, follow instructions for transport of skin biopsies for genetic/molecular testing, see Test catalog entry under Code:599.
2. Formalin-fixed paraffin embedded tissue: Send EITHER (a) formalin-fixed slides, OR (b) formalin-fixed tissue block:
(a) Instructions for slide specimens: 1 slide at 4-micron thickness stained with hematoxylin-and-eosin AND 10 unstained, non-baked slides at 10-micron thickness. Unstained slides can be on charged or uncharged slides. Note: In order to ensure that enough DNA is obtained, the minimum acceptable tissue area is 10 square millimeters when ten 10-micron slides are supplied (1 cubic millimeter of tissue). Tissue sections should contain as much lesional tissue as possible; to ensure detection of all types of mutations, there should be at least 10% lesional cells in the tissue area processed for DNA.
(b) Instructions for tissue block specimen: Provide complete formalin-fixed tissue block containing lesional tissue. If there is more than one tissue block, please provide the block that has the greatest amount of lesional tissue. Tissue block will be returned at completion of testing.
Unacceptable: Decalcified samples; tissue samples treated with fixatives other than formalin.
Also acceptable:
BLOOD:
- 10 mL whole blood in LAVENDER TOP EDTA or YELLOW TOP ACD tube and purified DNA from peripheral blood or cultured cells.
CULTURED CELLS:
- (2) T25 or (1) T75 flask (minimum 1-T25 flask)*.
*Prenatal testing requires concomitant testing for maternal cell contamination (see Online Test Guide Maternal Cell Contamination, Fetal [MCC] for ordering and specimen requirements)
Forms & Requisitions
Requisition Form and Ordering Instructions:
- Fill out a Genetics Requisition Form
- Check "Megalencephaly Panel"
Genetics Preauthorization Form (preauthorization is only done for providers who are external to the UW system).
Handling Instructions
Ship specimen at room temperature for overnight delivery.
Blood specimens can be held for up to 7 days before shipping if refrigerated.
Ship specimens to:
UW MEDICAL CENTER
LABORATORY MEDICINE - GENETICS LAB
1959 NE PACIFIC ST, ROOM NW220
SEATTLE, WA 98195-7110
Quantity
requested: Entire sample
minimum: For FFPE or skin biopsy, see above. 5 mL whole blood.
Processing
Blood: Refrigerate whole blood
Unacceptable Conditions: Frozen or clotted specimens
Stability (collection to initiation of testing): Ambient: 5 days; Refrigerated: 7 days; Frozen: Unacceptable
Purified DNA: Refrigerate DNA specimens. Frozen is acceptable.
Performance
LIS Dept Code
Genetics (GEN)
Performing Location(s)
| UW-MT |
Genetics
Attention: Genetics Lab Tel: 206-598–6429 M–F (7:30 AM–4:00 PM) Tel (EXOME only): 206-543-0459 |
Faculty |
|---|
Frequency
Results within 6 weeks, once sample arrives in the laboratory.
Available STAT?
No
Billing & Coding
CPT codes
Billing Comments
For additional test/billing information, see following page: MegaPlex™ CPT codes.
For pricing information, contact Client Support Services 206-520-4600 or 800-713-5198.
Billing and Insurance Pre-Authorization
We offer insurance pre-authorization services (preauthorization is only done for providers who are external to the UW system).
Email: gpab@uw.edu or call 1-855-320-4869 for more information.
LOINC
Interfaced Order Code
UOW2845