Epidermolysis Bullosa (EB)

NOW AVAILABLE! XomeDxSlice – EB

Using whole exome capture and sequencing, ALL of the known genes for the various forms of Epidermolysis Bullosa (Dystrophica, Simplex, Junctional) can be analyzed at one time, achieving substantial savings in both cost and time, with little loss of sensitivity. In most cases, this should now be the test of first choice for a new patient with the diagnosis of Epidermolysis Bullosa.

Epidermolysis Bullosa (EB) is an inherited skin and connective tissue disease that causes bullae (blisters) with mild trauma. The severity of the disorder depends on the layer of skin where the tissue separation occurs. In EB Simplex the blisters occur in the basal layer of the epidermis and do not leave scars. Most cases are caused by a mutation in either KRT5 or KRT14, and the disorder usually follows an autosomal dominant inheritance pattern, although autosomal recessive cases have been reported. Dystrophic EB (DEB) is a disorder with a range of severity from very severe to relatively mild. The blisters are caused by abnormalities of the anchoring fibrils, which are made up of type VII collagen, that attach the epidermis to the underlying dermis. Mutations in the COL7A1 gene can be autosomal dominant or recessive, and the blisters leave scars. Junctional EB is a heterogeneous disorder with the blisters occurring within or just above the lamina lucida (between the dermis and epidermis). In most cases, the blisters do not result in scarring. Junctional EB can be mild or severe and even lethal in the neonatal period; however surviving patients may improve with age. Mutations in several different genes can result in Junctional EB (virtually all recessive), including LAMA3, LAMB3, LAMC2, ITGA6, ITGB4, and COL17A1. There are also variant forms of EB in which other phenotypic features are found, including EB with pyloric atresia caused by mutations in the ITGA6, ITGB4 or PLEC1 gene, EB with muscular dystrophy (EB-MD) caused by mutations in the PLEC1 gene and variant forms of DEB in which only nails are affected (COL7A1). Additionally, there is considerable overlap in some features such as ITGB4 mutations causing EB without pyloric atresia but with associated urinary and gastrointestinal tract abnormalities. The variety of genes, and their relative complexity makes genetic testing challenging and a skin biopsy studied with antibodies to the various skin proteins by indirect immunofluorescence can help elucidate the type of EB and to inform the testing and mutation/gene assignment to be identified by XomeDxSlice - EB testing.

Tests Available

Forms and Documents

Test Details

CD151, CDSN, CHST8, COL17A1, COL7A1, CSTA, DSG1, DSG2, DSG3, DSG4, DSP, DST, EXPH5, FERMT1, GRIP1, ITGA3, ITGA6, ITGB4, KLHL24, KRT1, KRT10, KRT14, KRT5, LAMA3, LAMB3, LAMC2, MMP1, NID1, PKP1, PLEC, TGM5
  • Identification of the specific molecular basis of a hereditary blistering disorder
  • Recurrence risk assessment
  • Preparation for prenatal testing in future pregnancies

If an affected individual is found by XomeDxSlice-EB to have only a single mutation in a gene with recessive inheritance, deletion/duplication analysis of that gene can be performed at no additional cost.

Patient samples sent for XomeDxSlice will not be evaluated for secondary findings and therefore will not receive secondary findings as part of their result.

  • Next-Gen Sequencing

Ordering

707
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81406x2, 81479x8
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Varki et al., 2006 J Med Genet 43:641-52
  2. Varki et al., 2007 J Med Genet. 44:181-92
  3. Schumann et al., 2013 Br J Dermatol. Mar 18
  4. Charlesworth et al., 2013 Br J Dermatol. 168:808-814
  5. Yang et al., 2012 PediatrDermatol. 29:725-31
  6. Has et al., 2012 N Engl J Med. 366:1508-14
  7. Liu et al., 2012 J Invest Dermatol. 132:742-4
  8. Smith 2012 Br J Dermatol. 166:894-6
  9. Has et al., 2011 Hum Mutat. 32:1204-12
  10. Murase et al., 2011Acta DermVenereol. 91:730-1
  11. Uitto J. 2011 ActaDermVenereol. 91:259-61
  12. Almaani et al., 2011 ActaDermVenereol. 91:262-6
  13. Kiritsi et al., 2011 J Med Genet. 48:450-7
  14. Techanukul et al., 2011 ActaDermVenereol. 91:267-70
  15. Pigors et al., 2011 Hum Mol Genet. 20:1811-9
  16. Natsuga et al., 2010 Hum Mutat. 31:1687-98
  17. Hobbs et al., 2010 J Invest Dermatol. 130:2680-3
  18. Fine et al., 2008 J Am AcadDermatol. 58:931-50
  19. Intong et al., 2012 ClinDermatol. 30:70-7
  20. Sprecher E. 2010 DermatolClin. 2028:23-32
  21. Rezniczek et al., 2010 DermatolClin. 28:33-41, A series of review articles in DermatolClin. 2010 Jan;28
  22. Dang et al., 2008 ExpDermatol. 17:553-68
  23. Pfendner EG, Lucky AW Junctional Epidermolysis Bullosa. In: Pagon RA, Bird TC, Dolan CR, Stephens K, editors. GeneReviews
  24. Seattle (WA): University of Washington, Seattle; 1993-2008, Pfendner EG, Lucky AW: Dystrophic Epidermolysis Bullosa (November 2010) in: GeneReviews at GeneTests: Medical Genetics Information Resource [database online] Copyright, University of Washington,
  25. Pfendner EG & Lucky AW: Epidermolysis Bullosa with Pyloric Atresia (February 2013) in: GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2010. Available at http://www.gene