Junctional Epidermolysis Bullosa via the LAMA3 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7721 | LAMA3 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Junctional epidermolysis bullosa (JEB), one of the four major types of epidermolysis bullosa (EB), is a clinically and genetically heterogeneous skin/mucosa separation disorder characterized by blister formation induced by minimal mechanical trauma. Mutations in LAMA3 accounts for ~9% of pathogenic mutations reported in JEB. Generally, patients with Herlitz JEB (OMIM#226700), the neonatal lethal form JEB, carried null mutant LAMA3 alleles, while patients with Non-Herlitz JEB (OMIM#226650), the mild type JEB, had missense or splicing mutations (Kiritsi et al. J Med Genet 48:450-457, 2011; Intong et al. Clin Dermatol 30:70-77, 2012). In the severe cases, blisters can occur at birth in all parts of the body, erosions and granulations result in restrictions in oral, corneal, esophageal and lung tissues. Premature death is often caused by complications of dehydration, anemia and sepsis (Fine et al. J Am Acad Derm 58: 931-950, 2008; Pfendner et al. GeneReview, 2008; Laimer et al. Dermatol Clin 28:55–60, 2010). In addition, LAMA3 mutations were shown to cause laryngoonychocutaneous syndrome (LOCs or Shabbir OMIM#245660), characterized by skin blisters, nail dystrophy, ocular and laryngeal granulation.
Genetics
LAMA3 codes α chain of the Laminin-332 protein in skin. Mutations in the LAMA3 gene cause JEB and LOC, both of them are inherited in an autosomal recessive manner with full penetrance. Approximately 85% of reported mutations are truncating mutations. A funder mutation c.152dupG (also referred as 151insG) in exon 39 was found in LOC syndrome in Punjabi population (McLean et al. Hum Mol Gene 12:2395-409, 2003). The c.1981C>T, p.Arg661X in exon 54 (also referred as Arg650X by McGrath et al. Nat Genet 11:83, 1995) was mostly seen in Pakistani JEB patients.
Clinical Sensitivity - Sequencing with CNV PG-Select
Detection rate should be high in biopsy confirmed JEB patients with either reduced or absent Laminin5 expression, who have no mutations in LAMB3 or LAMC2 genes.
Testing Strategy
This test provides full coverage of all coding exons of the LAMA3 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Individuals with clinical features consistent with H-JEB, Non-Herlitz JEB and LOC. Individuals diagnosed with skin biopsy showing absent or reduced Laminin5 expression are preferred. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LAMA3.
Individuals with clinical features consistent with H-JEB, Non-Herlitz JEB and LOC. Individuals diagnosed with skin biopsy showing absent or reduced Laminin5 expression are preferred. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in LAMA3.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| LAMA3 | 600805 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Junctional Epidermolysis Bullosa | AR | 226700 |
| Laryngoonychocutaneous Syndrome | AR | 245660 |
| Non-Herlitz Junctional Epidermolysis Bullosa | AR | 226650 |
Related Tests
Citations
- Fine et al. (2008). "The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB." J Am Acad Derm 58(6):931-950. PubMed ID: 18374450
- Intong and Murrell. (2012). "Inherited epidermolysis bullosa: new diagnostic criteria and classification." Clin Dermatol 30(1):70-77. PubMed ID: 22137229
- Kiritsi et al. Molecular mechanisms of phenotypic variability in junctional epidermolysis bullosa. J Med Genet 48(7):450-457, 2011. PubMed ID: 21357940
- Laimer et al. Herlitz junctional epidermolysis bullosa. Dermatol Clin 28(1):55-60, 2010. PubMed ID: 19945616
- McGrath et al. Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa. Nat Genet 11(1):83-86, 1995. PubMed ID: 7550320
- McLean et al. An unusual N-terminal deletion of the laminin alpha3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome. Hum Mol Gene 12(18):2395-409, 2003. PubMed ID: 12915477
- Pfendner et al. Junctional Epidermolysis Bullosa. GeneReviews, 2008 PubMed ID: 20301304
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
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.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
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.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
Loading...
×
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.