Epidermolysis Bullosa NGS panel

Genes
(full
coding region):		 CD151, CDSN, CHST8, COL7A1, COL17A1, DSG1, DSP, DST, EXPH5, FERMT1, ITGA3, ITGB4, ITGA6, JUP, KRT1, KRT10, KRT14, KRT5, KRT9, LAMA3, LAMB3, LAMC2, MMP1, PLEC, PKP1, TGM5

List of diseases covered by the panel
Lab method: NGS panel with CNV analysis
TAT: 6-9 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of epidermolysis bullosa types/subtypes and other genetically/
phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Inherited epidermolysis bullosa (EB) is a group of genetic diseases characterized by skin fragility and blistering on the skin and mucous membranes in response to minor injury or friction. EB is clinically and genetically very heterogeneous. There are four main types with additional sub-types identified and within each type, one may be either mildly or severely affected. Classification into four main types considers the layer of skin in which blistering occurs: EB simplex (intraepidermal), junctional EB (within the lamina lucida of the basement membrane), dystrophic EB (below the basement membrane), and Kindler EB (mixed skin cleavage pattern). Stratification of EB into several subtypes (up-to-date 34 subtypes in total) takes account the clinical characteristics, the pattern of genetic inheritance, the expression of the altered protein, and the genetic alteration. Pathogenic variants in at least 18 genes that encode proteins in the epidermis, basement membrane or dermis have been associated with different subtypes of EB. The characteristic phenotype of the different types of EB is correlated to the gene that is altered. In turn, different genes can lead to very similar EB phenotypes.

The test covers the known genetic causes of EB types/subtypes and a range of other genetically/phenotypically related disorders.

Depending on the type of EB it could be inherited in an autosomal dominant or autosomal recessive pattern.

The combined prevalence of all types of EB is estimated to be 11 per 1,000,000 individuals. EB simplex is estimated to be 6 per 1,000,000 people, junctional EB 0,5 per 1,000,000 people, dystrophic EB 3,3 per 1,000,000 people, and Kindler’s EB is reported in approximately 250 individuals worldwide.

References:
Mariath LM, Santin JT, Schuler-Faccini L, Kiszewski AE. Inherited epidermolysis bullosa: update on the clinical and genetic aspects [published online ahead of print, 2020 Jul 8]. An Bras Dermatol. 2020; S0365-0596(20)30171-9. doi:10.1016/j.abd.2020.05.001. PMID: 32732072
Pfendner EG, Bruckner AL. Epidermolysis Bullosa Simplex. 1998 Oct 7 [Updated 2016 Oct 13]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1369/
Pfendner EG, Lucky AW. Dystrophic Epidermolysis Bullosa. 2006 Aug 21 [Updated 2018 Sep 13]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1304/
Pfendner EG, Lucky AW. Junctional Epidermolysis Bullosa. 2008 Feb 22 [Updated 2018 Dec 20]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1125/
Pfendner EG, Lucky AW. Epidermolysis Bullosa with Pyloric Atresia. 2008 Feb 22 [Updated 2017 Sep 7]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1157/
Youssefian L, Vahidnezhad H, Uitto J. Kindler Syndrome. 2016 Mar 3 [Updated 2016 Dec 1]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK349072/