+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



American Journal of Pathology 152(4): 935-941



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.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 068706769

Download citation: RISBibTeXText

PMID: 9546354


Related references

Compound heterozygosity for missense and nonsense mutations in the beta4 integrin gene underlies mild, nonlethal phenotype of epidermolysis bullosa with pyloric atresia. American Journal of Pathology 152(4): 935-941, 1998

Compound heterozygosity for novel nonsense/missense mutations in the beta4 integrin gene results in non-lethal junctional epidermolysis bullosa associated with pyloric atresia. British Journal of Dermatology 138(4): 741, 1998

Novel ITGB4 mutations in lethal and nonlethal variants of epidermolysis bullosa with pyloric atresia: missense versus nonsense. American Journal of Human Genetics 63(5): 1376-1387, 1998

Pyloric atresia-junctional epidermolysis bullosa syndrome: mutations in the integrin beta4 gene (ITGB4) in two unrelated patients with mild disease. British Journal of Dermatology 139(5): 862-871, 1998

Epidermolysis bullosa with pyloric atresia: novel mutations in the beta4 integrin gene (ITGB4). American Journal of Pathology 152(1): 157-166, 1998

Pyloric atresia-junctional epidermolysis bullosa syndrome showing novel 594insC/Q425P mutations in integrin beta4 gene (ITGB4). Experimental Dermatology 13(1): 61-64, 2004

Novel mutations in the ITGB4 gene associated with a mild phenotype in junctional epidermolysis bullosa with pyloric atresia: two siblings with differential expression of pyloric atresia. 2007

Compound heterozygosity for nonsense and missense mutations in the LAMB3 gene in nonlethal junctional epidermolysis bullosa. Journal Of Investigative Dermatology. 106(5): 1157-1159, 1996

Epidermolysis bullosa with congenital pyloric atresia: novel mutations in the beta 4 integrin gene (ITGB4) and genotype/phenotype correlations. Pediatric Research 49(5): 618-626, 2001

A Nonlethal Case of Junctional Epidermolysis Bullosa and Congenital Pyloric Atresia: Compound Heterozygosity in a Patient with a Novel Integrin Beta 4 Gene Mutation. Journal of Pediatrics 193: 261-264.E1, 2018

Epidermolysis bullosa with pyloric atresia Novel mutations in the beta4 integrin gene, phenotype/genotype correlations, and DNA-based prenatal testing. Journal of Dermatological Science 16(Suppl. 1): S36, 1998

A homozygous missense mutation in the cytoplasmic tail of beta4 integrin, G931D, that disrupts hemidesmosome assembly and underlies Non-Herlitz junctional epidermolysis bullosa without pyloric atresia?. Journal of Investigative Dermatology 114(5): 1061-1064, 2000

Mild phenotype of junctional epidermolysis bullosa with pyloric atresia due to a novel mutation of the ITGB4 gene. Journal of Dermatology 45(7): E203-E204, 2018

Splicing abnormality of integrin β4 gene (ITGB4) due to nucleotide substitutions far from splice site underlies pyloric atresia-junctional epidermolysis bullosa syndrome. Journal of Dermatological Science 78(1): 61-66, 2015

Pyloric atresia-junctional epidermolysis bullosa syndrome showing novel c.4505-4508insACTC mutations in integrin b4 gene (ITGB4). Turkish Journal of Pediatrics 57(4): 385-387, 2017