Disease relevance of ITGB4

• Novel ITGB4 mutations in lethal and nonlethal variants of epidermolysis bullosa with pyloric atresia: missense versus nonsense [1].
• Genomic organization of the integrin beta 4 gene (ITGB4): a homozygous splice-site mutation in a patient with junctional epidermolysis bullosa associated with pyloric atresia [2].

High impact information on ITGB4

• Expression of the alpha6 beta4 integrin is altered at the dermal-epidermal basement-membrane zone; recently, mutations in the corresponding genes (ITGA6 and ITGB4) have been disclosed in a limited number of patients, premature termination codons in both alleles being characteristic of lethal variants [1].
• These results confirm that ITGB4 mutations underlie EB-PA and show that missense mutations may lead to nonlethal phenotypes [1].
• The patients' neutrophils lack a membrane glycoprotein of mol wt 150,000 daltons (GP-150) on analysis by SDS-PAGE [3].
• Compound heterozygosity for missense (L156P) and nonsense (R554X) mutations in the beta4 integrin gene (ITGB4) underlies mild, nonlethal phenotype of epidermolysis bullosa with pyloric atresia [4].
• In this study, we demonstrate for the first time ITGB4 mutations in nonlethal phenotype of epidermolysis bullosa with congenital pyloric atresia [4].

Biological context of ITGB4

• Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta 4 integrin gene (ITGB4) and genotype/phenotype correlations [5].
• Nine novel single-nucleotide polymorphisms in the integrin beta4 (ITGB4) gene in the Japanese population [6].
• We identified nine single-nucleotide polymorphisms (SNPs) in the human integrin beta4 (ITGB4) gene (17q24-q25), which encodes a cell-surface receptor, by screening all exons and exon-intron boundaries [6].

Anatomical context of ITGB4

• It is concluded that GP150/GP85 is the rabbit homologue of human CD11/CD18, and that leukocyte-cell adhesion mediated by these glycoprotein complexes participates in acute and delayed inflammatory responses and leukocyte distribution in vivo [7].

Other interactions of ITGB4

• We review all previously published ITGA6 and ITGB4 mutation reports to help define genotype--phenotype correlation in this rare genodermatosis [8].
• At the molecular level the phenotype was caused by a novel 2 bp deletion 4733delCT in ITGB4, resulting in in-frame skipping of exon 36 and a deduced 50 amino acid deletion (1450-1499) within the third fibronectin type III repeat in the cytoplasmic domain of the integrin beta4 polypeptide [9].
• The mutation detection strategy included polymerase chain reaction amplification of each exon of ITGB4, followed by heteroduplex analysis and direct nucleotide sequencing [10].
• CD13 (GP150; aminopeptidase-N): predominant functional activity in blood is localized to plasma and is not cell-surface associated [11].

Analytical, diagnostic and therapeutic context of ITGB4

• Novel ITGB4 mutations in a patient with junctional epidermolysis bullosa-pyloric atresia syndrome and altered basement membrane zone immunofluorescence for the alpha6beta4 integrin [12].
• Although in both patients Northern blot analysis showed only a 50% reduction in the level of ITGB4 transcript, a complete lack (patient 1) or a strong reduction (patient 2) of beta4 immunoreactivity was observed in the skin [13].

References