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Early Infantile Epileptic Encephalopathy Sequencing Panel
- Summary and Pricing
- Clinical Features and Genetics
- Citations
- Methods
- Ordering/Specimens
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TEST METHODS
- NextGen Sequencing using PG-Select Capture Probes
- Deletion/Duplication Testing via Array Comparative Genomic Hybridization
NextGen Sequencing
| Test Code | Test Copy Genes | CPT Code Copy CPT Codes | |
|---|---|---|---|
| 1961 | ACY1 | 81479 | Add |
| ADSL | 81479 | ||
| ALDH7A1 | 81406 | ||
| ARFGEF2 | 81479 | ||
| ARHGEF9 | 81479 | ||
| ARX | 81404 | ||
| BCKDK | 81479 | ||
| CDKL5 | 81406 | ||
| CHD2 | 81479 | ||
| CHRNA2 | 81479 | ||
| CHRNA4 | 81405 | ||
| CHRNB2 | 81405 | ||
| CLN3 | 81479 | ||
| CLN5 | 81479 | ||
| CLN6 | 81479 | ||
| CLN8 | 81479 | ||
| CNTNAP2 | 81406 | ||
| CSTB | 81404 | ||
| CTSD | 81479 | ||
| CTSF | 81479 | ||
| DEPDC5 | 81479 | ||
| EPM2A | 81404 | ||
| FARS2 | 81479 | ||
| FOLR1 | 81479 | ||
| FOXG1 | 81404 | ||
| GABRA1 | 81479 | ||
| GABRB3 | 81479 | ||
| GABRG2 | 81405 | ||
| GAMT | 81479 | ||
| GNAO1 | 81479 | ||
| GOSR2 | 81479 | ||
| GRIN2A | 81479 | ||
| HCN1 | 81479 | ||
| KCNA2 | 81479 | ||
| KCNB1 | 81479 | ||
| KCNJ10 | 81404 | ||
| KCNQ2 | 81406 | ||
| KCNQ3 | 81479 | ||
| KCNT1 | 81479 | ||
| KCTD7 | 81479 | ||
| LGI1 | 81479 | ||
| MBD5 | 81479 | ||
| MECP2 | 81302 | ||
| MEF2C | 81479 | ||
| MFSD8 | 81479 | ||
| NHLRC1 | 81403 | ||
| NPRL2 | 81479 | ||
| NRXN1 | 81479 | ||
| PCDH19 | 81405 | ||
| PIGO | 81479 | ||
| PLCB1 | 81479 | ||
| PNKP | 81479 | ||
| PNPO | 81479 | ||
| POLG | 81406 | ||
| PPT1 | 81479 | ||
| PRRT2 | 81479 | ||
| RELN | 81479 | ||
| ROGDI | 81479 | ||
| SCARB2 | 81479 | ||
| SCN1A | 81407 | ||
| SCN1B | 81404 | ||
| SCN2A | 81479 | ||
| SCN8A | 81479 | ||
| SCN9A | 81479 | ||
| SLC13A5 | 81479 | ||
| SLC19A3 | 81479 | ||
| SLC25A22 | 81479 | ||
| SLC2A1 | 81405 | ||
| SLC35A2 | 81479 | ||
| SLC9A6 | 81406 | ||
| SPTAN1 | 81479 | ||
| ST3GAL3 | 81479 | ||
| ST3GAL5 | 81479 | ||
| STX1B | 81479 | ||
| STXBP1 | 81406 | ||
| SZT2 | 81479 | ||
| TBC1D24 | 81479 | ||
| TNK2 | 81479 | ||
| TPP1 | 81479 | ||
| TSC1 | 81406 | ||
| TSC2 | 81407 | ||
| WWOX | 81479 | ||
| Full Panel Price* | $790.00 | ||
| Test Code | Test Copy Genes | Total Price | CPT Codes Copy CPT Codes | |
|---|---|---|---|---|
| 1961 | Genes x (82) |
$790.00 | 81302, 81403, 81404(x6), 81405(x5), 81406(x8), 81407(x2), 81479(x59) | Add |
Pricing Comments
We are happy to accommodate requests for single genes or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered on our PGxome Custom Panel.
Targeted Testing
For ordering sequencing of targeted known variants, please proceed to our Targeted Variants landing page.
Turnaround Time
The great majority of tests are completed within 20 days.
Clinical Sensitivity
This panel includes genes causative for autosomal dominant, autosomal recessive and X-linked early infantile epileptic encephalopathy (EIEE). Extrapolating from previously published studies of next generation sequencing in large cohorts of patients with EIEE, we predict that our EIEE Panel will identify pathogenic variants more than 37% of EIEE cases with unknown cause (Lemke et al. 2012. PubMed ID: 22612257; Kodera et al. 2013. PubMed ID: 23662938; Carvill et al. 2013. PubMed ID: 23708187; Della Mina et al. 2015. PubMed ID: 24848745; Wang et al. 2014. PubMed ID:24818677; Ream et al. 2014. PubMed ID:25108116). In particular, clinical sensitivity for Autosomal Dominant Nocturnal Frontal Lobe Epilepsy is more than 25-35% while for autosomal dominant focal epilepsy, the sensitivity is more than 12-37% (Dibbens et al. 2013. PubMed ID:23542697; Ishida et al. 2013. PubMed ID:23542701; Picard et al. 2014. PubMed ID:24814846). This panel identifies pathogenic variants in 70-80% of Dravet syndrome patients (Ottman et al 2010. PubMed ID:20100225; Carvill et al 2014. PubMed ID:24623842; Gaily et al 2013. PubMed ID:23808377).
Del/Dup via aCGH
| Test Code | Test Copy Genes | Price | CPT Code Copy CPT Codes | |
|---|---|---|---|---|
| 600 | ACY1 | $990.00 | 81479 | Add |
| ADSL | $990.00 | 81479 | ||
| ALDH7A1 | $990.00 | 81479 | ||
| ARFGEF2 | $990.00 | 81479 | ||
| ARHGEF9 | $990.00 | 81479 | ||
| ARX | $990.00 | 81403 | ||
| BCKDK | $990.00 | 81479 | ||
| CDKL5 | $990.00 | 81405 | ||
| CHD2 | $990.00 | 81479 | ||
| CLN3 | $990.00 | 81479 | ||
| CLN5 | $990.00 | 81479 | ||
| CLN6 | $990.00 | 81479 | ||
| CLN8 | $990.00 | 81479 | ||
| CNTNAP2 | $990.00 | 81479 | ||
| CSTB | $990.00 | 81479 | ||
| CTSD | $990.00 | 81479 | ||
| CTSF | $990.00 | 81479 | ||
| EPM2A | $990.00 | 81479 | ||
| FARS2 | $990.00 | 81479 | ||
| FOLR1 | $990.00 | 81479 | ||
| FOXG1 | $990.00 | 81479 | ||
| GABRA1 | $990.00 | 81479 | ||
| GABRB3 | $990.00 | 81479 | ||
| GABRG2 | $990.00 | 81479 | ||
| GAMT | $990.00 | 81479 | ||
| GNAO1 | $990.00 | 81479 | ||
| GOSR2 | $990.00 | 81479 | ||
| GRIN2A | $990.00 | 81479 | ||
| KCNJ10 | $990.00 | 81479 | ||
| KCNQ2 | $990.00 | 81479 | ||
| KCNQ3 | $990.00 | 81479 | ||
| KCNT1 | $990.00 | 81479 | ||
| KCTD7 | $990.00 | 81479 | ||
| LGI1 | $990.00 | 81479 | ||
| MBD5 | $990.00 | 81479 | ||
| MECP2 | $990.00 | 81304 | ||
| MEF2C | $990.00 | 81479 | ||
| MFSD8 | $990.00 | 81479 | ||
| NHLRC1 | $990.00 | 81479 | ||
| NRXN1 | $990.00 | 81479 | ||
| PCDH19 | $990.00 | 81479 | ||
| PLCB1 | $990.00 | 81479 | ||
| PNKP | $990.00 | 81479 | ||
| PNPO | $990.00 | 81479 | ||
| POLG | $990.00 | 81479 | ||
| PPT1 | $990.00 | 81479 | ||
| RELN | $990.00 | 81479 | ||
| ROGDI | $990.00 | 81479 | ||
| SCARB2 | $990.00 | 81479 | ||
| SCN1A | $990.00 | 81479 | ||
| SCN1B | $990.00 | 81479 | ||
| SCN2A | $990.00 | 81479 | ||
| SCN8A | $990.00 | 81479 | ||
| SCN9A | $990.00 | 81479 | ||
| SLC19A3 | $990.00 | 81479 | ||
| SLC25A22 | $990.00 | 81479 | ||
| SLC2A1 | $990.00 | 81479 | ||
| SLC9A6 | $990.00 | 81479 | ||
| SPTAN1 | $990.00 | 81479 | ||
| ST3GAL3 | $990.00 | 81479 | ||
| ST3GAL5 | $990.00 | 81479 | ||
| STXBP1 | $990.00 | 81479 | ||
| SZT2 | $990.00 | 81479 | ||
| TBC1D24 | $990.00 | 81479 | ||
| TNK2 | $990.00 | 81479 | ||
| TPP1 | $990.00 | 81479 | ||
| TSC1 | $990.00 | 81405 | ||
| TSC2 | $990.00 | 81406 | ||
| Full Panel Price* | $1490.00 | |||
| Test Code | Test Copy Genes | Total Price | CPT Codes Copy CPT Codes | |
|---|---|---|---|---|
| 600 | Genes x (68) |
$1490.00 | 81304, 81403, 81405(x2), 81406, 81479(x63) | Add |
Pricing Comments
|
# of Genes Ordered |
Total Price |
|
1 |
$990 |
|
2-5 |
$1190 |
|
6-10 |
$1290 |
|
11-100 |
$1490 |
|
Over 100 |
Call for quote |
Turnaround Time
The great majority of tests are completed within 20 days.
Clinical Sensitivity
Large deletions or duplications that may not be detectable by sequencing have been reported in ARHGEF9, ARX, CDKL5, CHD2, FOXG1, GABRA1, GABRB3, GABRG2, GRIN2A, LGI1, MBD5, MECP2, MEF2C, PCDH19, PRRT2, SCN1A, SCN2A, SCN8A, SLC2A1, SLC9A6, SPTAN1, STX1B, STXBP1, TSC1 and TSC2 (Human Gene Mutation Database). Patients with an identifiable TSC pathogenic variant will have either a large deletion or duplication in up to 6% and 1% of cases in the TSC2 and TSC1 genes, respectively (Northrup et al. 2015. PubMed ID:20301399).
Clinical Features
Early Infantile Epileptic Encephalopathy (EIEE) is a clinically and genetically heterogeneous neurodevelopmental disorder. The key feature of EIEE is onset of frequent and/or severe seizures within the first few weeks of life (Noh et al. 2012. PubMed ID: 22342633). These seizures are often associated with febrile events and may be refractory to treatment with anti-epileptic drugs (AEDs). EIEE patients may also present with an abnormal EEG pattern, such as the characteristic burst-suppression pattern seen in Ohtahara syndrome (Khan and Al Baradie 2012. PubMed ID: 23213494). Intellectual disability and psychomotor delay are common features of many severe epileptic encephalopathies.
Genetics
The most common causes of EIEE in infants are structural brain abnormalities and inborn errors of metabolism (Sharma and Prasad 2013. PubMed ID: 23250121, Wilmshurst et al. 2015. PubMed ID: 26122601). However, in cases of EIEE in which structural or metabolic defects are lacking, genetic factors are being found to play an increasing role. EIEE is a genetically heterogeneous disorder; over 100 genes have been suggested to be involved in disease pathogenesis (Lemke et al. 2012. PubMed ID: 22612257). Many EIEE cases are sporadic, occurring in families with no prior history of seizure (Allen et al. 2013. PubMed ID: 23934111). Sporadic cases of EIEE are commonly caused by dominant, de novo pathogenic variants in neuronally expressed genes. EIEE can also be inherited in an autosomal recessive manner. In this panel, we sequence a total of 82 genes. This panel covers 22 genes which are related to epilepsy treatment including ALDH7A1, BCKDK, CHRNA4, DEPDC5, FOLR1, GAMT,GRIN2A, KCNQ2, KCNQ3, KCNT1, PCDH19, PNPO, POLG, PRRT2, SCN1A, SCN2A, SCN8A, SLC19A3, SLC2A1, STXBP1, TSC1 and TSC2 (see the table below).
41 genes in which dominant or X-linked pathogenic variants have been reported in the literature to be causative for EIEE. Several of these genes are involved in well-characterized syndromes in which seizures are a predominant feature (Ottman et al. 2010. PubMed ID: 20100225; Wilmshurst et al. 2015. PubMed ID: 26122601) such as:
Tuberous Sclerosis: TSC1 and TSC2
Infantile Spasm: ADSL, ARX, CDKL5, PNPO, MEF2C, SCN1A, SCN2A, STXBP1, TSC1, TSC2
Focal epilepsy: CHRNA4, CHRNB2, CHRNA2, CNTNAP2, DEPDC5, KCNT1, GRIN2A, LGI1, NPRL2, PCDH19, RELN, SCN1A, TBC1D24
Dravet Syndrome: SCN1A, SCN1B, GABRG2, SCN2A, SCN9A, PCDH19, GABRA1, STXBP1 and CHD2.
Ohtahara Syndrome: ARX, STXBP1, SCN2A, KCNQ2, KCNT1, SLC25A22, CDKL5, PNKP and SPTAN1.
Generalized (or genetic) Epilepsy with Febrile Seizures Plus (GEFS+): SCN1A, SCN1B, SCN2A, SCN9A), GABRG2, STX1B
DEPDC5-related epilepsy
Autosomal Dominant Nocturnal Frontal Lobe Epilepsy: CHRNA4, CHRNB2, CHRNA2, DEPDC5, KCNT1
Autosomal Dominant Lateral Temporal Lobe Epilepsy: LGI1, RELN
Benign Familial Neonatal or Infantile Seizures: KCNQ2, KCNQ3, PRRT2
Early-onset Absence Epilepsy: SLC2A1
Epilepsy and Mental Retardation Limited to Females: PCDH19
Rett Syndrome: MECP2, CDKL5, FOXG1
41 genes in which homozygous or compound heterozygous pathogenic variants have been reported to cause EIEE. Some of these genes are involved in well-characterized autosomal recessive conditions in which seizures are a predominant feature such as:
Neuronal Ceroid Lipofuscinosis: TPP1, PPT1, CLN3, CLN5, CLN6, MFSD8, CLN8, CTSF and KCTD7
Lafora Disease: EPM2A and NHLRC1
Selected metabolic disorders: FOLR1, GAMT, ALDH7A1, PNPO, SLC19A3
Selected mitochondrial disease: POLG, FARS2, SLC25A22
| Gene Name | Inherited Mode | Treatment Related References |
| ALDH7A1 | AR | Bennett et al. 2009. PubMed ID: 19128417 |
| BCKDK | AR | Oyarzabal et al. 2016. PubMed ID: 26809120 |
| CHRNA4 | AD | Kurahashi and Hirose 2015. PubMed ID: 20301348 |
| DEPDC5 | AD | Myers and Scheffer 2017. PubMed ID: 28406046 |
| FOLR1 | AR | Steinfeld et al. 2009. PubMed ID: 19732866 |
| GAMT | AR | Bodamer et al. 2009. PubMed ID: 19255414 |
| GRIN2A | AD | Pierson et al 2014. PubMed ID: 24839611 |
| KCNQ2 | AD | Sands et al. 2016. PubMed ID: 27888506 |
| KCNQ3 | AD | Sands et al. 2016. PubMed ID: 27888506 |
| KCNT1 | AD | Mikati et al 2015. PubMed ID: 26369628 |
| PCDH19 | AD | Trivisano et al 2015. PubMed ID: 25510386 |
| PNPO | AR | Bagci et al. 2007. PubMed ID: 18296573 |
| POLG | AR | Hynynen et al 2014. PubMed ID: 25065347 |
| PRRT2 | AD | Chou et al 2014. PubMed ID: 25520928 |
| SCN1A | AD | Miller and Sotero de Menezes 2007. PubMed ID: 20301494. |
| SCN2A | AD | Wolff et al 2017. PubMed ID: 28379373 |
| SCN8A | AD | Boerma et al 2016. PubMed ID: 26252990 |
| SLC19A3 | AR | Tabarki et al. 2013. PubMed ID: 23269594 |
| SLC2A1 | AD | Leen et al. 2010. PubMed ID: 20129935 |
| STXBP1 | AD | Dilena et al 2016. PubMed ID: 26212315 |
| TSC1 | AD | Palavra et al 2017. PubMed ID: 28386314 |
| TSC2 | AD | Palavra et al 2017. PubMed ID: 28386314 |
See individual gene test descriptions for information on molecular biology of gene products and spectra of pathogenic variants.
Testing Strategy
For this Next Generation Sequencing (NGS) test, sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization kit, followed by massively parallel sequencing of the captured DNA fragments.
For Sanger sequencing, polymerase chain reaction (PCR) is used to amplify targeted regions. After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.
This panel typically provides >99% coverage of all coding exons of the genes listed, plus ~10 bases of flanking noncoding DNA. We define coverage as ≥20X NGS reads or Sanger sequencing.
A full list of regions not covered by NGS or Sanger sequencing is available upon request.
Indications for Test
Testing is recommended for patients with symptoms of EIEE, notably those with infantile onset seizures with no clear structural or metabolic cause.
Genes
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
Related Tests
CONTACTS
Genetic Counselors
- Genetic Counselor Team - clinicaldnatesting@preventiongenetics.com
Geneticist
- Li Fan, MD, PhD, FCCMG, FACMG - li.fan@preventiongenetics.com
Citations
- Allen et al. 2013. PubMed ID: 23934111
- Bagci et al. 2007. PubMed ID: 18296573
- Bennett et al. 2009. PubMed ID: 19128417
- Bodamer et al. 2009. PubMed ID: 19255414
- Boerma et al 2016. PubMed ID: 26252990
- Carvill et al. 2013. PubMed ID: 23708187
- Carvill et al. 2014. PubMed ID: 24623842
- Chou et al 2014. PubMed ID: 25520928
- Della Mina et al. 2015. PubMed ID: 24848745
- Dibbens et al. 2013. PubMed ID: 23542697
- Dilena et al 2016. PubMed ID: 26212315
- Gaily et al. 2013. PubMed ID: 23808377
- Human Gene Mutation Database (Bio-base).
- Hynynen et al 2014. PubMed ID: 25065347
- Ishida et al. 2013. PubMed ID: 23542701
- Khan and Al Baradie. 2012. PubMed ID: 23213494
- Kodera et al. 2013. PubMed ID: 23662938
- Kurahashi and Hirose 2015. PubMed ID: 20301348
- Leen et al. 2010. PubMed ID: 20129935
- Lemke et al. 2012. PubMed ID: 22612257
- Mikati et al 2015. PubMed ID: 26369628
- Miller and Sotero de Menezes 2007. PubMed ID: 20301494
- Myers and Scheffer 2017 PubMed ID: 28406046
- Noh et al. 2012. PubMed ID: 22342633
- Northrup et al. 2015. PubMed ID: 20301399
- Ottman et al. 2010. PubMed ID: 20100225
- Oyarzabal et al. 2016. PubMed ID: 26809120
- Palavra et al 2017. PubMed ID: 28386314
- Picard et al. 2014. PubMed ID: 24814846
- Pierson et al 2014. PubMed ID: 24839611
- Ream and Mikati. 2014. PubMed ID: 25108116
- Sands et al. 2016. PubMed ID: 27888506
- Sharma and Prasad. 2013. PubMed ID: 23250121
- Steinfeld et al. 2009. PubMed ID: 19732866
- Tabarki et al. 2013. PubMed ID: 23269594
- Trivisano et al 2015. PubMed ID: 25510386
- Wang et al. 2014. PubMed ID: 24818677
- Wilmshurst et al. 2015. PubMed ID: 26122601
- Wolff et al 2017. PubMed ID: 28379373
Order Kits
TEST METHODS
- NextGen Sequencing using PG-Select Capture Probes
- Deletion/Duplication Testing via Array Comparative Genomic Hybridization
NextGen Sequencing using PG-Select Capture Probes
Test Procedure
We use a combination of Next Generation Sequencing (NGS) and Sanger sequencing technologies to cover the full coding regions of the listed genes plus ~10 bases of non-coding DNA flanking each exon. As required, genomic DNA is extracted from the patient specimen. For NGS, patient DNA corresponding to these regions is captured using an optimized set of DNA hybridization probes. Captured DNA is sequenced using Illumina’s Reversible Dye Terminator (RDT) platform (Illumina, San Diego, CA, USA). Regions with insufficient coverage by NGS are often covered by Sanger sequencing.
For Sanger sequencing, Polymerase Chain Reaction (PCR) is used to amplify targeted regions. After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.
Patient DNA sequence is aligned to the genomic reference sequence for the indicated gene region(s). All differences from the reference sequences (sequence variants) are assigned to one of five interpretation categories, listed below, per ACMG Guidelines (Richards et al. 2015).
(1) Pathogenic Variants
(2) Likely Pathogenic Variants
(3) Variants of Uncertain Significance
(4) Likely Benign Variants
(5) Benign Variants
Human Genome Variation Society (HGVS) recommendations are used to describe sequence variants (http://www.hgvs.org). Rare variants and undocumented variants are nearly always classified as likely benign if there is no indication that they alter protein sequence or disrupt splicing.
Analytical Validity
As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and 256 were insertions or deletions. About 65% of the variants were heterozygous and 35% homozygous. The insertions and deletions ranged in length from 1 to over 100 nucleotides.
In silico validation of insertions and deletions in 20 replicates of 5 genes was also performed. The validation included insertions and deletions of lengths between 1 and 100 nucleotides. Insertions tested in silico: 2200 between 1 and 5 nucleotides, 625 between 6 and 10 nucleotides, 29 between 11 and 20 nucleotides, 25 between 21 and 49 nucleotides, and 23 at or greater than 50 nucleotides, with the largest at 98 nucleotides. All insertions were detected. Deletions tested in silico: 1813 between 1 and 5 nucleotides, 97 between 6 and 10 nucleotides, 32 between 11 and 20 nucleotides, 20 between 21 and 49 nucleotides, and 39 at or greater than 50 nucleotides, with the largest at 96 nucleotides. All deletions less than 50 nucleotides in length were detected, 13 greater than 50 nucleotides in length were missed. Our standard NextGen sequence variant calling algorithms are generally not capable of detecting insertions (duplications) or heterozygous deletions greater than 100 nucleotides. Large homozygous deletions appear to be detectable.
Analytical Limitations
Interpretation of the test results is limited by the information that is currently available. Better interpretation should be possible in the future as more data and knowledge about human genetics and this specific disorder are accumulated.
When Sanger sequencing does not reveal any difference from the reference sequence, or when a sequence variant is homozygous, we cannot be certain that we were able to detect both patient alleles. Occasionally, a patient may carry an allele which does not amplify, due to a large deletion or insertion. In these cases, the report will contain no information about the second allele. Our Sanger and NGS Sequencing tests are generally not capable of detecting Copy Number Variants (CNVs).
We sequence all coding exons for each given transcript, plus ~10 bp of flanking non-coding DNA for each exon. Test reports contain no information about other portions of the gene, such as regulatory domains, deep intronic regions or any currently uncharacterized alternative exons.
In most cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.
Our ability to detect minor sequence variants due to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.
Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR.
Unless otherwise indicated, DNA sequence data is obtained from a specific cell-type (usually leukocytes from whole blood). Test reports contain no information about the DNA sequence in other cell-types.
We cannot be certain that the reference sequences are correct.
Rare, low probability interpretations of sequencing results, such as for example the occurrence of de novo mutations in recessive disorders, are generally not included in the reports.
We have confidence in our ability to track a specimen once it has been received by PreventionGenetics. However, we take no responsibility for any specimen labeling errors that occur before the sample arrives at PreventionGenetics.
Deletion/Duplication Testing via Array Comparative Genomic Hybridization
Test Procedure
Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.
Analytical Validity
PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.
Analytical Limitations
Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.
This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.
aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.
Breakpoints, if occurring outside the targeted gene, may be hard to define.
The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.
Order Kits
Ordering Options
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
REQUISITION FORM
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
SPECIMEN TYPES
WHOLE BLOOD
(Delivery accepted Monday - Saturday)
- Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
- For small babies, we require a minimum of 1 ml of blood.
- Only one blood tube is required for multiple tests.
- Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
- During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
- In cold weather, include an unfrozen ice pack in the shipping container as insulation.
- At room temperature, blood specimen is stable for up to 48 hours.
- If refrigerated, blood specimen is stable for up to one week.
- Label the tube with the patient name, date of birth and/or ID number.
DNA
(Delivery accepted Monday - Saturday)
- Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
- For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
- DNA may be shipped at room temperature.
- Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
- We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.
CELL CULTURE
(Delivery preferred Monday - Thursday)
- PreventionGenetics should be notified in advance of arrival of a cell culture.
- Culture and send at least two T25 flasks of confluent cells.
- Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
- Send specimens in insulated, shatterproof container overnight.
- Cell cultures may be shipped at room temperature or refrigerated.
- Label the flasks with the patient name, date of birth, and/or ID number.
- We strongly recommend maintaining a local back-up culture. We do not culture cells.
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