Dystrophic Epidermolysis Bullosa (DEB) via the COL7A1 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
967 COL7A1$3040.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Mutations in the COL7A1 gene can be found in ~95% of DEB patients diagnosed with skin biopsy (Pfendner et al. GeneReview, 2010).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 COL7A1$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity

To date, more than 600 distinct mutations have been documented in (Human Gene Mutation Database). Causative mutations include missense, nonsense, splicing mutations and small insertions/deletions. Only 10 large genome rearrangements involving COL7A1 were reported. In addition, one DEB case with maternal COL7A1 UPD was reported (Fassihi et al. J Invest Dermatol 126, 2039–2043, 2006).

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Clinical Features

Dystrophic Epidermolysis Bullosa (DEB) is a clinically heterogeneous skin separation disorder caused by mutations in the COL7A1 gene. DEB is characterized by blister formation induced by mild trauma. Autosomal recessive DEB (RDEB; OMIM#226600) can be further divided into severe generalized RDEB (also called Hallopeau-Siemens type) and generalized, not severe RDEB (also called non-Hallopeau-Siemens type). Severe generalized RDEB is the most severe form of DEB, where blisters may develop in the neonatal period and affect the whole body. Erosions and fusions can lead to restrictions in oral, corneal, esophageal, and lung tissue. Pseudosyndactly caused by extensive blistering and erosion can be a hallmark of severe generalized RDEB. Autosomal dominant DEB (DDEB; OMIM#131750) is the second most common subtype of epidermolysis bullosa, where the dystrophic nails may be the only manifestation in some of the DDEB patients, and blisters tend to be mild and localized to hands, knees and elbows. DEB patients are at high risk to develop squamous cell carcinoma (Fine et al. J Am Acad Dermatol 58: 931- 950, 2008; Pfendner et al. GeneReview, 2010; Intong et al. Clinics in Dermatology 30:70-77, 2012). In addition to DEB, mutations in COL7A1 also cause other DEB-related disorders including epidermolysis bullosa, BART type (OMIM#132000), epidermolysis bullosa pruriginosa (OMIM#604129), epidermolysis bullosa, pretibial (OMIM#131850), toenail dystrophy, isolated (OMIN#607523) and transient bullous of the newborn (OMIM#131705).


Collagen VII, a homotrimer of three α1 (VII) chains, is the major component of anchoring fibrils in the basal membrane zone of skin and cornea. It contains a central collagenous triple helical domain which is flanked by a large amino terminus (NC1) and a small carboxyl terminus (NC2) noncollagenous domain. Through the NC1 domain, Collagen VII interacts with various adhesive proteins including fibronectin, laminin 5 and type I and type IV collagens to bridge the dermo-epidermal connection (Keene et al. J of Cell Biology 104:611-621, 1987; Chen et al., J Bio Chem 272:14516-14522, 1997).  The penetrance of DEB is less than 100% (Hilal et al. Nat Genet 5: 287-293, 1993; Christiano et al. Nat Genet 4: 62, 1993; Pulkkinen and Uitto. Matrix Biology 18:29-42, 1999; Varki et al. J Med Genet 44:181–192, 2007 and Pfendner et al. GeneReview, 2010). To date, more than 600 distinct mutations have been documented in (Human Gene Mutation Database). Causative mutations include missense, nonsense, splicing mutations and small insertions/deletions. Only 10 large genome rearrangements involving COL7A1 were reported. In addition, one DEB case with maternal COL7A1 UPD was reported (Fassihi et al. J Invest Dermatol 126, 2039–2043, 2006). Approximately 75% of the DDEB mutations occur in exons 73–75; while RDEB are caused by truncated mutations scattered throughout COL7A1 (Varki et al., 2007; Pfendner et al. GeneReview, 2010).

Testing Strategy

Collagen VII is coded by the COL7A1 gene on chromosome 3p21.31. Testing involves the PCR amplifications from genomic DNA and bidirectional Sanger DNA sequencing of the coding exons 1-118 and ~10 bp of adjacent noncoding sequences. We will also sequencing any single exon (test#100) or pair of exons (test#200) in family members of patients with known mutations or to confirm research results.

Indications for Test

Individuals with clinical features consistent with DEB and DEB-related disorders. Individuals diagnosed by a skin biopsy showing abnormal or reduced Collagen VII expression are preferred (Varki et al., 2007).


Official Gene Symbol OMIM ID
COL7A1 120120
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Genetic Counselors
  • Chen, M. et al. (1997). "Interactions of the amino-terminal noncollagenous (NC1) domain of type VII collagen with extracellular matrix components. A potential role in epidermal-dermal adherence in human skin." J Biol Chem 272(23): 14516-22. PubMed ID: 9169408
  • Christiano, A. M. et al. (1993). "A missense mutation in type VII collagen in two affected siblings with recessive dystrophic epidermolysis bullosa." Nat Genet 4(1): 62-6.  PubMed ID: 8513326
  • Fassihi et al. (2006). J Invest Dermato 126, 2039–2043.
  • Fassihi, H. et al. (2006). "Complete maternal isodisomy of chromosome 3 in a child with recessive dystrophic epidermolysis bullosa but no other phenotypic abnormalities." J Invest Dermatol 126(9): 2039-43. PubMed ID: 16710310
  • 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
  • Hilal, L. et al. (1993). "A homozygous insertion-deletion in the type VII collagen gene (COL7A1) in Hallopeau-Siemens dystrophic epidermolysis bullosa." Nat Genet 5(3): 287-93. PubMed ID: 8275094
  • Human Gene Mutation Database (Bio-base).
  • Intong and Murrell. (2012). "Inherited epidermolysis bullosa: new diagnostic criteria and classification." Clin Dermatol 30(1):70-77. PubMed ID: 22137229
  • Keene, D. R.  et al. (1987). "Type VII collagen forms an extended network of anchoring fibrils." J Cell Biol 104(3): 611-21. PubMed ID: 3818794
  • Pfendner, E. G. and A. W. Lucky (2010). "Dystrophic Epidermolysis Bullosa." GeneReviews. PubMed ID: 20301481
  • Pulkkinen and Uitto. (1999). "Mutation analysis and molecular genetics of epidermolysis bullosa." Matrix Biol. 18(1): 29-42. PubMed ID: 10367729
  • Varki, et al. Epidermolysis bullosa. II. (2007). "Type VII collagen mutations and phenotype-genotype correlations in the dystrophic subtypes." J Med Genet 44(3):181-192. PubMed ID: 16971478
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all 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 for example 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 and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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.

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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.
  • 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.


(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.


(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.


(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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