Epidermolysis Bullosa Simplex

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. While XomeDxSlice-EB is appropriate for most cases of EB, for patients with a clinical diagnosis of Dowling-Meara, Koebner, Weber-Cockayne or other suspected forms of EB Simplex, it may be more cost-effective and provide increased sensitivity to perform test #168 (KRT5/14 Hot Spots) first . If this test is negative, reflex to XomeDxSlice- EB is available, and a discount for the cost of test #168 will be applied.

EBS is a heterogeneous disorder with a spectrum of severity from very mild blistering localized to hands and feet to more severe generalized blistering, which can be severe and even life threatening especially in the neonatal period. There are also variants such as EBS with mottled pigmentation, which are associated with a two known mutations in the keratin 5 gene. Autosomal dominant and recessive forms have been reported and de novo mutations are not uncommon. Diagnosis of EBS should be made with a skin biopsy studied by immunohistochemistry and or electron microscopy before mutation detection is undertaken. GeneDx requests that the referring physician contact Beutner Laboratories in Buffalo, NY (716-838-0549) to arrange for immunohistochemical analysis of a skin biopsy from the affected individual.

Mutations in the keratin genes are identified first by examination of mutational hotspots from genomic DNA from buccal swabs or a blood sample. If no mutation is found on this preliminary screen, the remainder of the coding sequence of the KRT5 and KRT14 gene will be analyzed. Such sequencing analysis of the KRT5 and KRT14 genes will identify 75-80% of EBS mutations. Additionally, sequencing of the coding region and splice sites of the PLEC1 gene is offered in two tiers. Tier 1 comprises exons 31 and 32, while Tier 2 includes sequence analysis of the remaining 30 exons. The sensitivity of PLEC1 testing in patients with EBS has not been well established since the number of cases described is small. The remaining 20% of EBS patients may have mutations in other undisclosed genes. Once a mutation is identified in an affected individual, mutation-specific testing of other family members and prenatal diagnosis is available.

Tests Available

Forms and Documents

Test Details

KRT14
  • Confirmation of a clinical diagnosis
  • Recurrence risk calculation
  • Prenatal diagnosis in families with an affected child and defined mutation
  • Capillary Sequencing

Ordering

1682
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
Yes
Yes
  • 757.39 Other Accessory skin tags, congenital, Congenital scar, Epidermolysis bullosa, Keratoderma (congenital)
* For price inquiries please email zebras@genedx.com

References

  1. Rugg et al. J Invest Dermatol 2006
  2. Koss-Harnes D et. al. 1997 Exp Dermatol. 6:41-8
  3. Koss-Harnes D et. al. 2002 J Invest Information Sheet on Epidermolysis Bullosa Simplex Page 3 of 3 © GeneDx Revision Date: 12/10 Dermatol. 118:87-93
  4. Pfendner EG, et al 2005. J Invest Dermatol 125:239-243
  5. Je?ábková et al. British J of Derm 162:1004-1013, 2009
  6. Arin et al. British J of Dermatol, 162:1365-1369, 2009
  7. Smith F.2003. Am J Clin Dermatol. 4:347-64

Forms and Documents

Test Details

KRT5
  • Confirmation of a clinical diagnosis
  • Recurrence risk calculation
  • Prenatal diagnosis in families with an affected child and defined mutation
  • Capillary Sequencing

Ordering

1681
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
Yes
Yes
  • 757.39 Other Accessory skin tags, congenital, Congenital scar, Epidermolysis bullosa, Keratoderma (congenital)
* For price inquiries please email zebras@genedx.com

References

  1. Jeřábková et al. British J of Derm 162:1004-1013, 2009
  2. Arin et al. British J of Dermatol, 162:1365-1369, 2009
  3. Koss-Harnes D et. al. 2002 J Invest Simplex Dermatol. 118:87-93
  4. Koss-Harnes D et. al. 1997 Exp Dermatol. 6:41-8
  5. Rugg et al. J Invest Dermatol 2006
  6. Pfendner EG, et al 2005. J Invest Dermatol 125:239-243
  7. Smith F.2003. Am J Clin Dermatol. 4:347-64

Forms and Documents

Test Details

KRT14, KRT5
  • Confirmation of a clinical diagnosis
  • Genetic counseling and recurrence risk calculation
  • Capillary Sequencing

Ordering

168
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
Yes
Yes
  • 757.39 Other Accessory skin tags, congenital, Congenital scar, Epidermolysis bullosa, Keratoderma (congenital)
* For price inquiries please email zebras@genedx.com

References

  1. Jeřábková et al. British J of Derm 162:1004-1013, 2009
  2. Koss-Harnes D et. al. 2002 J Invest Dermatol. 118:87-93
  3. Arin et al. British J of Dermatol, 162:1365-1369, 2009
  4. Koss-Harnes D et. al. 1997 Exp Dermatol. 6:41-8.
  5. Rugg et al. J Invest Dermatol 2006
  6. Pfendner EG, et al 2005. J Invest Dermatol 125:239-243
  7. Smith F.2003. Am J Clin Dermatol. 4:347-64

Forms and Documents

Test Details

PLEC1
  • Confirmation of a clinical diagnosis
  • Recurrence risk calculation
  • Prenatal diagnosis in families with an affected child and defined mutation
  • Capillary Sequencing

Ordering

3482
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 757.39 Other Accessory skin tags, congenital, Congenital scar, Epidermolysis bullosa, Keratoderma (congenital)
* For price inquiries please email zebras@genedx.com

References

  1. Pfendner E et.al. 2005 Exp Dermatol. 14:241-9
  2. Mellerio JE et. al. 1997 Br J Dermatol. 137:898-906
  3. Kunz M et. al. 2000 J Invest Dermatol. 114:376-80
  4. Bauer JW et. al. 2001 Am J Pathol.158:617- 25
  5. Charlesworth A et. al. 2003 J Invest Dermatol. 121:1344-8
  6. Rezniczek GA et. al. 2003 Hum Mol Genet. 12:3181-94
  7. Elliott CE et. al. 1997 Genomics 42:115-25
  8. Gache et al 1998 J Invest Dermatol 111:914-6
  9. Dolan et al 1993. Am J Med Genet 47:395-400
  10. Lepinard et al 2000 Prenat Diagn 20:70-5
  11. Azarian et al 2006 Prenat Diagn 26:57-9
  12. Koss-Harnes D et. al. 2002 J Invest Dermatol. 118:87-93
  13. Koss-Harnes D et. al. 1997 Exp Dermatol. 6:41-8
  14. McMillan JR et. al. 2007 Muscle Nerve.35:24-35
  15. Takahashi Y et. al. 2005 J Dermatol Sci. 37:87-93
  16. Koss- Harnes D et. al. 2004 Acta Derm Venereol. 84:124-31
  17. Schröder R et. al 2002 J Neuropathol Exp Neurol. 61:520-30
  18. Schara U et. al. 2004 Eur J Pediatr. 163:218-22
  19. Shimizu H et. al. 1999 J Am Acad Dermatol. 41:950-6
  20. Takizawa Y et. al. 1999 J Invest Dermatol. 112:109-12
  21. Dang M et. al 1998. Lab Invest. 78:195-204
  22. Pulkkinen L, et. al. 1996 Hum Mol Genet. 5:1539-46
  23. Smith FJ et. al. 1996 Nat Genet.13:450-7
  24. McLean WH et. al..1996 Genes Dev.10:1724-35
  25. Pfendner E, Uitto J. 2005 J Invest Dermatol. 124:111-5
  26. Rouan F et. al.2000 J Invest Dermatol. 114:381-7
  27. Nakamura H et. al. 2005 J Mol Diagn.7:28-35
  28. Sawamura D et. al 2007 J Invest Dermatol. 127:1537-40
  29. Chavanas S et. al. 1996 J Clin Invest. 98:2196-200
  30. Shimizu H et. al 1999 Arch Dermatol Res. 291:531-7

Forms and Documents

Test Details

PLEC1
  • Confirmation of a clinical diagnosis
  • Recurrence risk calculation
  • Prenatal diagnosis in families with an affected child and defined mutation
  • Capillary Sequencing

Ordering

3481
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Pfendner E et.al. 2005 Exp Dermatol. 14:241-9
  2. Lepinard et al 2000 Prenat Diagn 20:70-5
  3. Azarian et al 2006 Prenat Diagn 26:57-9.
  4. Koss-Harnes D et. al. 2002 J Invest Dermatol. 118:87-93
  5. Schröder R et. al 2002 J Neuropathol Exp Neurol. 61:520-30
  6. Schara U et. al. 2004 Eur J Pediatr. 163:218-22
  7. Koss- Harnes D et. al. 2004 Acta Derm Venereol. 84:124-31
  8. Takahashi Y et. al. 2005 J Dermatol Sci. 37:87-93
  9. Rezniczek GA et. al. 2003 Hum Mol Genet. 12:3181-94
  10. Mellerio JE et. al. 1997 Br J Dermatol. 137:898-906
  11. Takizawa Y et. al. 1999 J Invest Dermatol. 112:109-12
  12. Kunz M et. al. 2000 J Invest Dermatol. 114:376-80
  13. Bauer JW et. al. 2001 Am J Pathol.158:617- 25
  14. Charlesworth A et. al. 2003 J Invest Dermatol. 121:1344-8
  15. Elliott CE et. al. 1997 Genomics 42:115-25
  16. Gache et al 1998 J Invest Dermatol 111:914-6
  17. Dolan et al 1993. Am J Med Genet 47:395-400
  18. Koss-Harnes D et. al. 1997 Exp Dermatol. 6:41-8
  19. McMillan JR et. al. 2007 Muscle Nerve.35:24-35
  20. Shimizu H et. al. 1999 J Am Acad Dermatol. 41:950-6
  21. Shimizu H et. al 1999 Arch Dermatol Res. 291:531-7
  22. Dang M et. al 1998. Lab Invest. 78:195-204
  23. Chavanas S et. al. 1996 J Clin Invest. 98:2196-200
  24. Pulkkinen L, et. al. 1996 Hum Mol Genet. 5:1539-46
  25. Smith FJ et. al. 1996 Nat Genet.13:450-7
  26. Pfendner E, Uitto J. 2005 J Invest Dermatol. 124:111-5
  27. Rouan F et. al.2000 J Invest Dermatol. 114:381-7
  28. McLean WH et. al..1996 Genes Dev.10:1724-35
  29. Nakamura H et. al. 2005 J Mol Diagn.7:28-35
  30. Sawamura D et. al 2007 J Invest Dermatol. 127:1537-40

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