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. While XomeDxSlice-EB is appropriate for most cases of EB, for patients with a clinical diagnosis of Dowling-Meara, Koebner, Weber-Cockayne or other suspected forms of EB Simplex, it may be more cost-effective and provide increased sensitivity to perform test #168 (KRT5/14 Hot Spots) first . If this test is negative, reflex to XomeDxSlice- EB is available, and a discount for the cost of test #168 will be applied.
EBS is a heterogeneous disorder with a spectrum of severity from very mild blistering localized to hands and feet to more severe generalized blistering, which can be severe and even life threatening especially in the neonatal period. There are also variants such as EBS with mottled pigmentation, which are associated with a two known mutations in the keratin 5 gene. Autosomal dominant and recessive forms have been reported and de novo mutations are not uncommon. Diagnosis of EBS should be made with a skin biopsy studied by immunohistochemistry and or electron microscopy before mutation detection is undertaken. GeneDx requests that the referring physician contact Beutner Laboratories in Buffalo, NY (716-838-0549) to arrange for immunohistochemical analysis of a skin biopsy from the affected individual.
Mutations in the keratin genes are identified first by examination of mutational hotspots from genomic DNA from buccal swabs or a blood sample. If no mutation is found on this preliminary screen, the remainder of the coding sequence of the KRT5 and KRT14 gene will be analyzed. Such sequencing analysis of the KRT5 and KRT14 genes will identify 75-80% of EBS mutations. Additionally, sequencing of the coding region and splice sites of the PLEC1 gene is offered in two tiers. Tier 1 comprises exons 31 and 32, while Tier 2 includes sequence analysis of the remaining 30 exons. The sensitivity of PLEC1 testing in patients with EBS has not been well established since the number of cases described is small. The remaining 20% of EBS patients may have mutations in other undisclosed genes. Once a mutation is identified in an affected individual, mutation-specific testing of other family members and prenatal diagnosis is available.