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pubmed:abstractText |
Mutations in the genes encoding the subunit polypeptides of the alpha6beta4 integrin (ITGA6 and ITGB4, respectively) have been previously demonstrated in patients with a lethal form of epidermolysis bullosa with congenital pyloric atresia (OMIM #226730). In this study, we demonstrate for the first time ITGB4 mutations in nonlethal phenotype of epidermolysis bullosa with congenital pyloric atresia. Specifically, the proband was shown to be a compound heterozygote for a missense mutation (L156P) and a nonsense mutation (R554X). The leucine substitution by proline was shown to affect a residue, which was precisely conserved in different human, rodent, and drosophila integrin-beta polypeptides, and consequently disrupts the alpha-helix formation of the polypeptide segment as determined by Garnier alpha-helicity plot. The nonsense mutation in another allele was accompanied by undetectable levels of the corresponding mRNA transcript, as determined by reverse transcription-polymerase chain reaction. The presence of a missense mutation, when combined with a premature termination codon mutation, may explain the milder blistering tendency of the skin in this patient.
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pubmed:affiliation |
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, and Jefferson Institute of Molecular Medicine, Philadelphia, Pennsylvania 19107, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Case Reports,
Research Support, Non-U.S. Gov't
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