Megalencephaly Panel

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General Information

Lab Name
Megalencephaly Panel
Lab Code
MEGPX
Epic Ordering
Megalencephaly Panel
Description

Megalencephaly Panel is useful for the evaluation of patients with a suspected megalencephaly syndrome. The panel (version 2) uses next- generation sequencing to detect most mutations in ABCC9, AKT1, AKT2, AKT3, BRWD3, CCND2, CDKN1C, CUL4B, DEPDC5, DNMT3A, EED, EZH2, GLI3, GNAQ, GNAS, GPC3, HEPACAM, KCNJ8, KIF7, MED12, MLC1, MTOR, NFIA, NFIX, NSD1, PIK3CA, PIK3R2, PTCH1, PTEN, RAB39B, RIN2, RNF135, SETD2, STRADA, TBC1D7, TSC1, and TSC2. The assay completely sequences all exons of these genes AND detects large deletions, duplications and mosaicism. For patients with suspected hereditary epilepsy, see Epileptic Encephalopathy Panel [EPIPX].

Genes Tested (Assay Version 2)

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
CUL4B Syndromic X linked mental retardation 17236139,25385192
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
HEPACAM Megalencephalic Leukoncephalopathy with Subcortical Cysts 20301707
KCNJ8 Cantu syndrome 24700710
KIF7 Macrocephaly, multiple epiphyseal dysplasia and distinctive facies 22587682
MED12 Opitz-Kaveggia syndrome 20301719
MLC1 Megalencephalic Leukoncephalopathy with Subcortical Cysts 20301707
MTOR Megalencephaly, hemimegalencephaly, focal cortical dysplasia 25799227
NFIA Macrocephaly and intellectual disability 19763616,26997977
NFIX Overgrowth and macrocephaly 25118028
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
PIK3R2 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, polymicrogyria 22729224,26520804
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
RAB39B X-linked intellectual disability and macrocephaly with autism 20159109
RIN2 MACS syndrome (macrocephaly, alopecia, cutis laxa and scoliosis) 19631308
RNF135 Overgrowth and macrocephaly 17632510
SETD2 Overgrowth and macrocephaly 24852293
STRADA PMSE syndrome (polyhydramnios, megalencephaly, symptomatic epilepsy) 17522105
TBC1D7 Megalencephaly with intellectual disability, autosomal recessive 23687350,24515783
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
Forms & Requisitions

Requisition Form and Ordering Instructions:

  1. Fill out a Genetics Requisition Form
  2. Check "Megalencephaly Panel"

Genetics Preauthorization Form (preauthorization is only done for providers who are external to the UW system).

Synonyms
ABCC9, AKT1, AKT2, AKT3, BRWD3, CCND2, CDKN1C, CUL4B, Chiari malformation, DEPDC5, DNMT3A, EED, EZH2, GLI3, GNAQ, GNAS, GPC3, HEPACAM, KCNJ8, KIF7, Klippel Trenauney Weber syndrome, MED12, MLC1, MTOR, MegaPlex, NFIA, NFIX, NSD1, PIK3CA, PIK3R2, PTCH1, PTEN, RAB39B, RIN2, RNF135, SETD2, STRADA, TBC1D7, TSC1, TSC2, autism, cortical brain malformation, developmental delay, hemihypertrophy, hydrocephalus, macrocephaly, next-generation sequencing, overgrowth syndrome, polydactyly, seizures, syndactyly, tuberous sclerosis, ventriculomegaly
Components

Interpretation

Method

Next-generation sequencing.

This assay sequences all exons of multiple genes associated with megalencephaly syndrome. A total of 1.1Mb of DNA is sequenced and the average coverage ranges from 320 to >1,000 sequencing reads per bp. Genomic regions are captured using biotinylated RNA oliognucleotides (SureSelect), prepared in paired-end libraries with ~200 bp insert size, and sequenced on an Illumina HiSeq2500 instrument with 100 bp read lengths, in a modification of a procedure described by Pritchard et al. 2012. Large deletions and duplications are detected using methods described by Nord et al. 2011.

Reference Range
See individual components
Ref. Range Notes

No mutations detected.

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
Guidelines

Ordering & Collection

Specimen Type
Skin biopsy/Cultured fibroblasts, FFPE Tissue, Peripheral Blood, purified DNA
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) T23 or (1) T75 flask (minimum 1-T25 flask)*.

*Prenatal testing requires concomitant testing for maternal cell contamination (see Online Test Guide Maternal Cell Contamination [MCC] for ordering and specimen requirements)

Forms & Requisitions

Requisition Form and Ordering Instructions:

  1. Fill out a Genetics Requisition Form
  2. 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 cultured fibroblasts, see above. 5 mL whole blood

Processing

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
Clinical lab, Room NW220
University of Washington Medical Center
1959 NE Pacific Street
Seattle, WA 98195

Tel: 206-598–6429 M–F (7:30 AM–4:00 PM)
Fax: 206-598–0304
Lab email: genelab@uw.edu

Tel (EXOME only): 206-543-0459

Manager

Rebecca Gaulin, rgaulin@uw.edu

Genetic Counselors

Angela Jacobson, MS, LGC agibson@uw.edu
Sarah Paolucci, MA, MS, LGC, spaolucc@uw.edu
Jenna Huey, MS, LGC, jlhuey@uw.edu
Sandra Coe, MS,LGC, scoe20@uw.edu
Dru Leistritz, MS, LGC, dru2@uw.edu (EXOME testing only)

Variant Review Scientist

Ankita Jhuraney, PhD

Faculty

Colin C. Pritchard, MD, PhD
Brian H. Shirts, MD, PhD
Christina Lockwood, PhD, DABCC
Stephen Salipante, MD, PhD
Eric Konnick, MD, MS
Niklas Krumm, MD,PhD
Vera Paulson, MD, PhD
Jillian Buchan, PhD, FACMG

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: ngsbill@uw.edu or call 1-855-320-4869 for more information.

Genetics Preauthorization Form

LOINC
51966-0