Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) is an autosomal recessive blistering disease including lethal and non-lethal variants due to mutations in ITGB4 and ITGA6. It is unclear whether PA is caused directly by the mutations in these genes or by other factors. Skin biopsies from patients with JEB were processed for immunofluorescence mapping. When staining for integrin beta4 or alpha6 was absent or reduced, ITGB4 was screened for mutations. A review of known mutations of ITGB4 and the phenotypes of patients with JEB-PA was undertaken. Three novel ITGB4 mutations were identified in 3 families with JEB-PA: 2 splice-site and one insertion mutation. Two families with lethal phenotypes (EB-050 and EB-049) were due to combinations of premature termination codons and missense mutations (658delC/R252C and 3903dupC/G273D, respectively). The third family EB-013 has 2 JEB affected siblings; a brother with PA and a sister without PA. Both were homo notzygous for ITGB4 264G>A/3111-1G>A. Two cases had no gastrointestinal symptoms or signs of PA. PA is an inconstant feature of the subtype of epidermolysis bullosa known as JEB-PA. It is most likely that multiple factors influence the development of PA and its presence is not predictive of a poor outcome. It is possible that institutions that do not routinely screen immunofluore notscence mapping for integrin alpha6beta4 staining in the absence of PA are missing this form of epidermolysis bullosa.

Background: The clinical utility of serum k and l free light chains (FLC) for the diagnosis and prognosis of plasma cell proliferative disorders is well established. We assessed the analytical performance of the N Latex FLC assays and compared it with the Freelite TM assays.

Epidermolysis bullosa simplex is a heterogeneous group of inherited bullous disorders due to mutations in keratins 5 and 14. We report two different mutations in keratin 14 at codon 119 of the helix initiation peptide, each with different phenotypic expression. One, a sporadic case that clinically resembles Dowling-Meara epidermolysis bullosa simplex, resulted from conversion of methionine to threonine (M119T). The other, a multigeneration family with the Koebner phenotype, resulted from a previously unreported methionine to valine substitution (M119V). We suggest that loss of hydrophobicity during conversion of methionine to threonine is responsible for the more severe presentation of the first family, whereas maintenance of the hydrophobic nature of the amino acid with conversion to valine resulted in a less severe variant of epidermolysis bullosa simplex. Although most prior mutations in the highly conserved boundary motif of the alpha-helix have resulted in the Dowling-Meara subtype, our findings confirm that it is not always possible to predict the epidermolysis bullosa simplex severity on the basis of the location of the mutation along the keratin polypeptide. The specific amino acid substitution may be more critical in some cases.

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