Epidermolysis Bullosa with Pyloric Atresia via the ITGB4 Gene

Epidermolysis Bullosa with Pyloric Atresia (OMIM# #226730) is skin separation disorder characterized by congenital blistering, skin atrophy, and skin fragility. Other features in this syndrome include congenital pyloric atresia, ureterovesical stenosis, pyelonephrosis, esophageal atresia, congenital cutis aplasia, and arthrogryposis (Fine et al. J Am Acad Derm 58:931-950, 2008; Varki et al. J Med Genet 43: 641-652, 2006;  Pfendner et al., GeneReviews, 2013).

Epidermolysis bullosa with pyloric atresia is an autosomal recessive disorder caused by mutations in the ITGB4, ITGA6, and PLEC genes. Intergrin, beta 4 protein,  encoded by ITGB4 (OMIM#147557), is a receptor for laminin and belongs to the integrin family that regulates the cell-cell adhesion and cell-matrix adhesion. Intergrin, beta 4 and intergrin, alpha 6 form a heterodimer complex (α6β4 integrin protein) in the hemidesmosome of epithelial cells, which help to hold the layers of skin together. To date, 72 distinct mutations have been documented in HGMD (Human Gene Mutation Database) including missense, nonsense, small deletions, insertions and splicing mutations. A common mutation c.182G>A (p.Cys61Tyr) has been found in the Hispanic population (Pfendner et al., GeneReviews, 2013). Only two large deletions within ITGB4 were reported (Birnbaum RY et al. Am J Med Genet A 146A(8):1063-1066).

ITGB4 mutations account for ~80% of epidermolysis bullosa with pyloric atresia cases diagnosed by skin biopsy (Pfendner et al., GeneReviews, 2013). Only two large deletions within ITGB4 have been reported (Birnbaum RY et al. Am J Med Genet A 146A(8):1063-1066).

This test provides full coverage of all coding exons of the ITGB4 gene 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 full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).