Epidermolysis Bullosa, Junctional with Muscular Dystrophy

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.

There are three variant phenotypic forms of EB due to plectin mutations; EB with pyloric atresia or pyloric stenosis (EB-PA), EB with muscular dystrophy (EB-MD), and a mild autosomal dominant EBS form known as EBS-Ogna. In all three forms, blistering begins in the neonatal period and continues throughout life. Blisters are usually generalized and may range from mild to severe. However, aside from blistering, the forms diverge based on the extracutaneous findings. EB-PA is often lethal in the newborn period; however surviving patients may show less severe blistering as they age. In these children pyloric atresia requires surgical intervention in the neonatal period. In EB-MD blistering is usually milder, and muscular dystrophy may appear in late childhood to adulthood. EBS-Ogna is a rare autosomal dominant variant of EB in which mutations on one allele have been described in extended family members. In all three of these variants that are caused by plectin mutations the tissue separation (blister) occurs just above the lamina lucida at the level of the hemidesmosome. Plectin staining of a skin biopsy may be reduced or absent consistent with plectin mutations. Muscle biopsies may also be stained for plectin in cases where MD is suspected and will show reduced or absent plectin staining. In rare cases, EB-PA was identified based on ultrasound abnormalities in fetuses of families with no family history. Subsequent molecular testing revealed the presence of ITGB4 or ITGA6 mutations, although this has not been described in EB cases with plectin defects.

Tests Available

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