Download Test Information Sheet

GeneDx
207 Perry Parkway
Gaithersburg, MD 20877
Phone: 301-519-2100
Fax: 301-519-2892
E-mail: [email protected]
www.genedx.com
Test Information Sheet
COL7A1 Gene Analysis in
Dystrophic Epidermolysis Bullosa (DEB)
Mendelian Inheritance in Man Numbers: Dystrophic Epidermolysis Bullosa (120120), Hallopeau Siemens
form of DEB (226600), Pasini form of DEB (131750), pretibial form of DEB (131850), pruriginosa form
(604129), epidermolysis bullosa with congenital absence of skin and deformity of nails (132000), transient
bullous dermolysis of the newborn (131705)
Clinical features:
In this clinical type of EB, blistering usually begins in the neonatal period and may continue throughout life
or may be transient (transient bullous dermolysis of the newborn). Blisters may be generalized and include
oral and esophageal lesions in the severest form (Hallopeau-Siemens) or may be localized to the elbows and
knees, and/or hands and feet in the milder forms. In addition, dystrophic nails are also often present.
Dystrophic EB is not usually lethal but in the severest cases infants may succumb to infection or other
complications. The lifetime risk of squamous cell carcinoma in patients with the Hallopeau-Siemens form is
over 90%. In affected individuals the tissue separation (blister) occurs below the lamina densa. Anchoring
fibrils may be reduced or absent. Collagen VII staining may be reduced or absent in the more severe forms or
may appear relatively normal in the milder forms.
Inheritance pattern:
Dystrophic EB is due to mutations in only the COL7A1 gene, although there is significant variability in the
severity of the phenotype in different individuals. DEB may have either an autosomal recessive or autosomal
dominant inheritance pattern, depending upon the mutation and its location. The recurrence risk for couples
with a child affected with the recessive form is 25%. In the dominant forms recurrence risk is 50% to
offspring of an affected parent, although rarely unaffected carrier individuals have been observed (Pfendner
personal communication). The recurrence risk to unaffected extended family members is low in the absence
of consanguinity. Many de novo dominant mutations have been reported and the determination of recurrence
risk is dependent upon identification of the mutation(s) and inheritance pattern. Risk of recurrence in
subsequent pregnancies after a child is born with a de novo dominant mutation is 2-5%.
Reasons for referral:
1. Confirmation of a clinical diagnosis
2. Genetic counseling and recurrence risk calculation
3. Prenatal diagnosis in families with an affected child and defined mutation
Test method:
Sequencing of the COL7A1 genes is offered. Using genomic DNA obtained from the submitted biological
material, bi-directional sequence of the coding region and splice junctions of the COL7A1 gene (118 coding
exons) is analyzed where over 90% of mutations have been identified in DEB patients with clinically and
histologically confirmed disease. Mutation found in the first person of a family to be tested is confirmed by
repeat analysis using sequencing, restriction fragment analysis, or another appropriate method. Sequencing
of specific exons may be recommended for specific ethnic groups or phenotypes, especially in confirmed or
suspected dominant dystrophic EB, after consultation with the EB specialist at GeneDx ([email protected],
610,-574-3479). Deletion of specific exons has been reported rarely. Testing for deletions is available after
full COL7A1 gene screening at GeneDx, where one or both mutations are not detected and biopsy
confirming the diagnosis of DEB has been performed.
Information Sheet on Dystrophic Epidermolysis Bullosa
Page 1 of 2
GeneDx Revision Date: 05/2013
Test sensitivity:
Sequencing of the COL7A1 gene is expected to identify mutations in greater than 90% of patients with
clinical and histologic features of DEB. The underlying genetic cause of DEB in the remaining cases may
be due to mutations in the promoter, deep into introns, or large deletions not identifiable by our methods. A
skin biopsy studied with appropriate collagen VII antibodies and/or electron microscopy to confirm the
diagnosis of DEB is strongly recommended prior to pursuing genetic analysis.
Mutation spectrum:
All types of mutations have been reported in the COL7A1 gene and result in reduced or absent
collagen VII protein. Generally, the severest forms of the disease are the result of nonsense
mutations or out of frame insertions or deletions on both alleles while milder forms may be due to
splicing mutations or missense mutations on one or both alleles. However, numerous exceptions
have been reported.
Specimen Requirements and Shipping/Handling:
 Blood: A single tube with 1-5 mL whole blood in EDTA. Ship overnight at ambient temperature, using
a cool pack in hot weather. Specimens may be refrigerated for 7 days prior to shipping.
 Buccal Brushes: As an alternative to blood, use a GeneDx buccal kit (others not accepted). Submit by
mail. Buccal brushes are not accepted on children under 6 months of age.

Prenatal Diagnosis: For prenatal testing for a known mutation in the COL7A1 gene, please refer to the
specimen requirements table on our website at: http://www.genedx.com/test-catalog/prenatal/. Ship
specimen overnight at ambient temperature, using a cool pack in hot weather.
Required Forms:
 Sample Submission (Requisition) Form – complete all pages
 Payment Options Form or Institutional Billing Instructions
For test codes, prices, CPT codes, and turn-around-times, please refer to the “Dystrophic Epidermolysis
Bullosa” page on our website: www.genedx.com
References: 1. Jarvikallio A et al., 1997 Hum Mutat 10:338.
2. Rouan F, et al., 1998 J Invest Dermatol 111:1210.
3. Fine J-D et al., 2000 J Am Acad Dermatol 42:1051-106
4. Anton-Lamprecht & Gedde-Dahl, 2002. Epidermolysis bullosa. In: Rimoin DL, Connor JM, Pyeritz RE, Korf BR, eds.
Principles and Practice of Medical Genetics. 4th ed. London: Churchill-Livingston 2002, 3810-3897.
5. Varki et al., 2007 J Med Genet 44: 181-192.
Information Sheet on Dystrophic Epidermolysis Bullosa
Page 2 of 2
GeneDx Revision Date: 05/2013