Decode DEB Sponsored Testing Program

Epidermolysis Bullosa (EB) is a clinically and genetically heterogeneous skin separation disorder. Based on the level of skin separation, it can be divided into four major subgroups: dystrophic epidermolysis bullosa (DEB), junctional epidermolysis bullosa (JEB), epidermolysis bullosa simplex (EBS), and Kindler syndrome (Fine et al. 2014. PubMed ID: 24690439).

Dystrophic Epidermolysis Bullosa (DEB) is characterized by blister formation induced by mild trauma, which has two types: autosomal recessive and autosomal dominant. Autosomal recessive DEB (RDEB) is the most severe form of DEB, where blisters may develop in the neonatal period and affect the whole body. Erosions and fusions can lead to restrictions in oral, corneal, esophageal, and lung tissue. Pseudosyndactly caused by extensive blistering and erosion can be a hallmark of RDEB. Autosomal dominant DEB (DDEB) is the second most common subtype of epidermolysis bullosa, where the dystrophic nails may be the only manifestation in some DDEB patients, and blisters tend to be mild and localized to hands, knees and elbows. DEB patients are at high risk to develop squamous cell carcinoma (Fine et al. 2008. PubMed ID: 18374450; Pfendner et al. 2016. PubMed ID: 20301481; Intong et al. 2012. PubMed ID: 22137229).

Junctional epidermolysis bullosa (JEB) is one of the four major types of epidermolysis bullosa (EB), in which blisters develop within the mid portion or junction (lamina lucida). Morphologically, it can be divided into generalized JEB and localized JEB, which includes junctional epidermolysis bullosa and epidermolysis bullosa with pyloric atresia (Fine et al. 2014. PubMed ID: 24690439). Other features in this syndrome include congenital pyloric atresia, ureterovesical stenosis, pyelonephrosis, esophageal atresia, congenital cutis aplasia, and arthrogryposis (Fine et al. 2008. PubMed ID: 18374450; Varki et al. 2006. PubMed ID: 16473856; Pfendner et al. 2014. PubMed ID: 20301304).

Epidermolysis Bullosa Simplex (EBS) is a skin separation disorder characterized by congenital blistering, skin atrophy, and skin fragility caused by minor physical trauma (Fine et al. 2008. PubMed ID: 18374450).

Kindler syndrome is the fourth major type of epidermolysis bullosa, characterized by congenital blistering, skin atrophy, photosensitivity, and skin fragility (Fine et al. 2008. PubMed ID: 18374450). Other features include palmoplantar keratoderma, gingival erosions, and ocular, esophageal, gastrointestinal and urogenital involvement. Patients with Kindler syndrome are also at risk to develop mucocutaneous malignancy (Lai-Cheong et al. 2010. PubMed ID: 19945624).

Dystrophic epidermolysis bullosa (DEB) is mainly caused by pathogenic variants in the COL7A1 gene. To date, more than 700 distinct pathogenic variants have been documented in (Human Gene Mutation Database) including missense, nonsense, splicing variants and small insertions/deletions. Only 14 large genome rearrangements involving COL7A1 were reported. Approximately 75% of the dominant DEB pathogenic variants occur in exons 73-75; while recessive DEB are caused by truncated pathogenic variants scattered throughout COL7A1 (Varki et al. 2006. PubMed ID: 16473856; Pfendner et al. 2016. PubMed ID: 20301481).

Junctional epidermolysis bullosa (JEB) is an autosomal recessive disorder caused by pathogenic variants in the LAMA3, COL17A, LAMB3, and LAMC2 genes. Pathogenic variants in LAMB3, LAMA3, COL17A1, and LAMC2 account for ~70%, 12%, 9%, and 9% of pathogenic variants reported in JEB cases, respectively.

Epidermolysis bullosa simplex (EBS): EBS is caused by variants in KRT5 and KRT14, which are usually inherited in an autosomal dominant manner; however, a few recessive cases have also been reported. Biallelic pathogenic variants in TGM5 also cause EBS (Pfendner et al. 2016. PubMed ID: 20301481). Pathogenic variants in DST cause autosomal recessive epidermolysis bullosa simplex and autosomal recessive hereditary sensory and autonomic neuropathy, type VI (Groves et al. 2010. PubMed ID: 20164846; Liu et al. 2012. PubMed ID: 22113475; Turcan et al. 2017. PubMed ID: 28558912).

Kindler syndrome is an autosomal recessive disorder caused by pathogenic variants in FERMT1. To date, more than 80 distinct pathogenic variants have been documented (Human Gene Mutation Database). The majority are truncating variants. Only 8 large deletions involving FERMT1 have been reported (Lai-Cheong et al. 2010. PubMed ID: 19945624; Chmel et al. 2015. PubMed ID: 26083552).

This test is performed using next generation sequencing with additional Sanger sequencing as necessary. This panel provides 99.9% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

This program is available to patients residing in the United States, including Puerto Rico, who meet the following eligibility requirements:

• The patient must have clinical symptoms consistent with epidermolysis bullosa (EB).
• The patient must not have had prior genetic testing for EB in a clinical laboratory

For familial testing, the patient does not have to display clinical symptoms.

SPECIMEN REQUIREMENTS

Whole Blood

Collect 3 ml - 5 ml of whole blood in EDTA (purple top tube) or ACD (yellow top tube), minimum 1 ml for small infants.

Saliva

Oragene™ or GeneFiX™ Saliva Collection kit used according to manufacturer instructions. DNA from saliva specimens is invariably contaminated with microbial and food DNA, which can impact specimen quality and may result in delayed testing and/or the need for a second specimen.

OCD-100 Buccal Swab

OCD-100 Buccal Swab used according to manufacturer instructions.

Buccal

Specimens may be shipped at room temperature.

Specimen collection kits: Buccal specimen collection kits, which contain the TRF and the shipping label, may be requested through the kit order form or via the online order form.

SHIPPING AND HANDLING INSTRUCTIONS

Label all specimen containers with the patient's name, date of birth, and/or ID number. At least two identifiers should be listed on specimen containers. Specimen deliveries are accepted Monday-Saturday for all specimen types. Holiday schedules will be posted on our website at least one week prior to major holidays.