List of diseases covered by Epidermolysis Bullosa NGS panel

Published 02/01/2019

List of diseases covered by
Epidermolysis Bullosa NGS panel

Gene Condition
CD151 Nephropathy with pretibial epidermolysis bullosa and deafness
CDSN Hypotrichosis 2; Peeling skin syndrome 1
CHST8 Peeling skin syndrome 3
COL7A1 Epidermolysis bullosa dystrophica, AD;
Epidermolysis bullosa dystrophica, AR; Epidermolysis bullosa pruriginosa;
Epidermolysis bullosa, pretibial; Toenail dystrophy, isolated;
Transient bullous of the newborn; EBD, Bart type
COL17A1 Epidermolysis bullosa, junctional, localisata variant;
Epithelial recurrent erosion dystrophy
DSG1 Erythroderma, congenital, with palmoplantar keratoderma,
hypotrichosis, and hyper IgE; Keratosis palmoplantaris striata I, AD
DSP Epidermolysis bullosa, lethal acantholytic;
Keratosis palmoplantaris striata II; Skin fragility-woolly hair syndrome;
Cardiomyopathy, dilated, with woolly hair and keratoderma;
Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis
DST Epidermolysis bullosa simplex, autosomal recessive 2
EXPH5 Epidermolysis bullosa, nonspecific, autosomal recessive
FERMT1 Kindler syndrome
ITGA3 Interstitial lung disease, nephrotic syndrome,
and epidermolysis bullosa, congenital
ITGB4 Epidermolysis bullosa of hands and feet;
Epidermolysis bullosa, junctional, non-Herlitz type;
Epidermolysis bullosa, junctional, with pyloric atresia
ITGA6 Epidermolysis bullosa, junctional, with pyloric stenosis
JUP Naxos disease
KRT1 Epidermolytic hyperkeratosis;
Ichthyosis histrix, Curth-Macklin type;
Ichthyosis, cyclic, with epidermolytic hyperkeratosis;
Keratosis palmoplantaris striata III; Palmoplantar keratoderma, epidermolytic;
Palmoplantar keratoderma, nonepidermolytic
KRT10 Epidermolytic hyperkeratosis;
Ichthyosis with confetti; Ichthyosis, cyclic, with epidermolytic hyperkeratosis
KRT14 Dermatopathia pigmentosa reticularis;
Epidermolysis bullosa simplex, Dowling-Meara type;
Epidermolysis bullosa simplex, Koebner type;
Epidermolysis bullosa simplex, recessive 1;
Epidermolysis bullosa simplex, Weber-Cockayne type;
Naegeli-Franceschetti-Jadassohn syndrome
KRT5 Dowling-Degos disease 1;
Epidermolysis bullosa simplex, Dowling-Meara type;
Epidermolysis bullosa simplex, Koebner type;
Epidermolysis bullosa simplex, recessive 1;
Epidermolysis bullosa simplex, Weber-Cockayne type;
Epidermolysis bullosa simplex-MCR; Epidermolysis bullosa simplex-MP
KRT9 Palmoplantar keratoderma, epidermolytic
LAMA3 Epidermolysis bullosa, generalized atrophic benign;
Epidermolysis bullosa, junctional, Herlitz type;
Laryngoonychocutaneous syndrome
LAMB3 Epidermolysis bullosa, junctional, Herlitz type;
Epidermolysis bullosa, junctional, non-Herlitz type;
Amelogenesis imperfecta, type IA
LAMC2 Epidermolysis bullosa, junctional, Herlitz type;
Epidermolysis bullosa, junctional, non-Herlitz type
MMP1 Epidermolysis bullosa dystrophica,
autosomal recessive, modifier of
PLEC Epidermolysis bullosa simplex with nail dystrophy;
Epidermolysis bullosa simplex with muscular dystrophy;
Epidermolysis bullosa simplex with pyloric atresia;
Epidermolysis bullosa simplex, Ogna type
PKP1 Ectodermal dysplasia/skin fragility syndrome
TGM5 Peeling skin syndrome 2

Epidermolysis Bullosa NGS panel

Published 02/01/2019

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/