Program eligibility
This test is indicated for patients in the US presenting with idiopathic pain/neuropathy, and/or autonomic dysfunction, or stroke, whose physician suspects a potential causative genetic condition.
About the test
- This panel contains GAA, GLA, and IDUA as well as some genes associated with neuropathies and/or cerebrovascular disorders. If a blood sample (as opposed to saliva) is submitted, enzyme assay for glucocerebrosidase (Gaucher) will be performed in parallel due to complexities with GBA1 sequencing by NGS.
- If two variants in GAA are found (whether pathogenic, likely pathogenic or variants of uncertain significance), this test will reflex to acid α-glucosidase enzyme analysis.
- If a variant in GLA is found (whether pathogenic, likely pathogenic or variant of uncertain significance), this test will reflex to α-galactosidase A enzyme analysis and lyso-Gb3 analysis.
- If two variants in IDUA are found (whether pathogenic, likely pathogenic or variants of uncertain significance), this test will reflex to acid α-L-iduronidase enzyme analysis.
- If glucocerebrosidase enzyme is low, this test will reflex to GBA1 sequencing and Lyso-Gb1 analysis.
Sample requirements
Enzyme assay: Dried blood spots are preferred, but whole blood is also acceptable.
Gene sequencing: Dried blood spots (DBS) are preferred, but whole blood is also acceptable. A saliva sample can be used if only gene sequencing is being ordered.
Bundled testing (Enzyme assay with reflex to sequencing and biomarker): Dried blood spots (DBS) are preferred, but whole blood is also acceptable. A saliva sample cannot be used for enzyme assay or biomarker measurement.
Methodology
Panel methodology:
Sequencing is performed on genomic DNA using a targeted sequence capture method to enrich for the genes of interest. Direct sequencing of the amplified captured regions is performed using 2X150bp reads on next generation sequencing (NGS) systems. A base is considered to have sufficient coverage at 20X and an exon is considered fully covered if all coding bases plus three nucleotides of flanking sequence on either side are covered at 20X or more. A list of these regions, if any, is available upon request. Alignment to the human reference genome (GRCh37) is performed and annotated variants are identified in the targeted region. Variants reviewed have a minimum coverage of 8X and an alternate allele frequency of 20% or higher. Indel and single nucleotide variants (SNVs) may be confirmed by Sanger sequence analysis before reporting at director discretion. This assay cannot detect variants in regions of the exome that are not covered, such as deep intronic, promoter and enhancer regions, areas containing large numbers of tandem repeats, and variants in mitochondrial DNA. Copy number variation (CNV) analysis detects deletions and duplications; in some instances, due to the size of the exons, sequence complexity, or other factors, not all CNVs may be analyzed or may be difficult to detect. When reported, copy number variant size is approximate. Actual breakpoint locations may lie outside of the targeted regions. CNV analysis will not detect tandem repeats, balanced alterations (reciprocal translocations, Robertsonian translocations, inversions, and balanced insertions), methylation abnormalities, triploidy, and genomic imbalances in segmentally duplicated regions. This assay is not designed to detect mosaicism; possible cases of mosaicism may be investigated at the discretion of the laboratory director. Tertiary data analysis is performed using SnpEff v5.0 and Revvity Omics' internal ODIN v.1.01 software. CNV and absence of heterozygosity are assessed using Bionano’s NxClinical v6.1 software.
GBA1 testing methodology:
Long-range PCR is performed to capture the true genomic sequences for the gene of interest from this individual’s genomic DNA to avoid pseudogene contaminants. PCR product is utilized to prepare for the library and further sequenced using Next-generation sequencing (NGS) with 150 base pair paired-end reads. Indels and SNVs are confirmed by Sanger sequence analysis before reporting at the director’s discretion. This analysis cannot detect variants in regions not analyzed such as promoters, deep intronic regions, or long repetitive regions. Copy number variation (CNV) analysis is assessed using MLPA or manual reviewing of NGS reads using IGV viewer. This analysis cannot determine the location or orientation of a duplication. Copy neutral gene conversion or fusion, complex rearrangement, or large deletion including the entire GBA gene with breakpoint(s) outside the targeted region may not be detected by this assay. This assay is not designed to detect mosaicism; possible cases of mosaicism may be investigated at the discretion of the laboratory director.
Enzyme assay:
Enzyme activity is measured on dried blood spots (DBS) via Flow Injection Tandem Mass Spectrometry (FIA/MS/MS).
Turn-Around-Times (TAT)
Enzyme assay: 3 days
Gene sequencing: 3 weeks
Genes tested
AARS1, ACVRL1, ADA2, AIFM1, ATL1, ATL3, ATP7A, BSCL2, CBS, COL4A1, COL4A2, CTC1, DNAJB2, DNM2, DNMT1, DST, DYNC1H1, ENG, EPHB4, FGD4, GAA, GARS1, GDAP1, GDF2, GJB1, GLA, GUCY1A1, HSPB1, HSPB8, HTRA1, KIF1A, KRIT1, LITAF, LMNA, LRSAM1, MFN2, MMUT, MORC2, MPZ, MTMR2, NDRG1, NEFL, NGF, NOTCH3, NPC1, NTRK1, OTC, PCCA, PCCB, PMM2, PMP22, POLG, PRDM12, PRX, RAB7A, RASA1, REEP1, RETREG1, SBF2, SCN10A, SCN11A, SCN5A, SCN9A, SLC25A46, SLC2A10, SLC52A2, SMARCAL1, SPTLC1, SPTLC2, TREX1, TTR, WNK1, YARS1
References
- Finsterer J, Löscher WN, Wanschitz J, Iglseder S. Orphan Peripheral Neuropathies. J Neuromuscul Dis. 2021;8(1):1-23. doi:10.3233/JND-200518
- Boehme AK, Esenwa C, Elkind MS. Stroke Risk Factors, Genetics, and Prevention. Circ Res. 2017 Feb 3;120(3):472-495. doi: 10.1161/CIRCRESAHA.116.308398. PMID: 28154098; PMCID: PMC5321635.
- Ortiz A, Germain DP, Desnick RJ, Politei J, Mauer M, Burlina A, Eng C, Hopkin RJ, Laney D, Linhart A, Waldek S, Wallace E, Weidemann F, Wilcox WR. Fabry disease revisited: Management and treatment recommendations for adult patients. Mol Genet Metab. 2018 Apr;123(4):416-427. doi: 10.1016/j.ymgme.2018.02.014. Epub 2018 Feb 28. PMID: 29530533.
- Marieke Biegstraaten, Eugen Mengel, Laszlo Maródi, Milan Petakov, Claus Niederau, Pilar Giraldo, Derralyn Hughes, Mirando Mrsic, Atul Mehta, Carla E. M. Hollak, Ivo N. van Schaik, Peripheral neuropathy in adult type 1 Gaucher disease: a 2-year prospective observational study, Brain, Volume 133, Issue 10, October 2010, Pages 2909–2919.
- Güngör D, Schober AK, Kruijshaar ME, Plug I, Karabul N, Deschauer M, van Doorn PA, van der Ploeg AT, Schoser B, Hanisch F. Pain in adult patients with Pompe disease: a cross-sectional survey. Mol Genet Metab. 2013;109(4):371-376.
- Yuen A, Dowling G, Johnstone B, Kornberg A, Coombs C. Carpal tunnel syndrome in children with mucopolysaccaridoses. J Child Neurol. 2007 Mar;22(3):260-3. doi: 10.1177/0883073807300528. PMID: 17621494.
How to order
Step 1
Test selection and place order
Step 2
Specimen collection and shipment
Step 3
Get results
How to order
1. Test selection and place order
Select the correct test for your patient, and fill out The Lantern Project Requisition Form.
- Please make sure that all sections are completed, and that the patient has signed the informed consent form.
2. Specimen collection and shipment
- Obtain a sample for testing from the patient using one of the provided Revvity Omics test packs. If you do not have a kit available in your office, please contact us here and we can have one sent out to your office.
- Ensure that the patient sample is labeled with the patient’s name and date of birth.
- Please note that all biochemical assays require a dried blood spot sample or whole blood. Step-by-step instructions for collecting a sample can be found here.
- Samples may be submitted without a collection kit by following the guidelines for specimen requirements and completing the requisition form.
- Package the patient sample, informed consent form, and test requisition form back into the test kit, and utilize the included pre-paid shipping label to return the kit to Revvity Omics for processing.
- As a patient’s clinical presentation is an essential part of fully interpreting genetic test results, we ask that you kindly include any applicable medical records or clinical notes with the sample at the time of test submission.
3. Get results
Once Revvity Omics receives the sample, you will receive phone call to report abnormal findings, with a written report to follow within the established turnaround time for the ordered test. Bundled tests will be reported together in one comprehensive result.
The Lantern Project is not intended to and should not interfere in any way with a health care professional’s or patient’s independent judgment and freedom of choice in the treatment options for these diseases. Health care professionals and patients should always consider the full range of treatment options and select those most appropriate for the individual patient.
This testing service has not been cleared or approved by the U.S. Food and Drug Administration. Testing services may not be licensed in accordance with the laws in all countries. The availability of specific test offerings is dependent upon laboratory location. The content on this page is provided for informational purposes only, not as medical advice. It is not intended to substitute the consultation, diagnosis, and/or treatment provided by a qualified licensed physician or other medical professionals.