Alpha 6 beta 4 integrin abnormalities in junctional epidermolysis bullosa with pyloric atresia.
Junctional epidermolysis bullosa with pyloric atresia (JEB-PA) (MIM 226730) is an autosomal recessive disorder resulting from mutations in the genes encoding alpha 6 beta 4 integrin (ITGA6 and ITGB4). Clinically, it is characterized by mucocutaneous fragility and gastrointestinal atresia, which most commonly affects the pylorus. Additional features of JEB-PA include involvement of the urogenital tract, aplasia cutis and failure to thrive. While most affected individuals have a poor prognosis resulting in death in infancy, others have milder clinical features and a better prognosis. We report two previously undescribed homozygous ITGB4 mutations in two unrelated families, which resulted in severe skin blistering, pyloric atresia and lethality in infancy. Delineation of the mutations was used to undertake DNA-based prenatal diagnosis in subsequent pregnancies at risk for recurrence in both families. We review all previously published ITGA6 and ITGB4 mutation reports to help define genotype--phenotype correlation in this rare genodermatosis.
Ashton
G H
GH
Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
Sorelli
P
P
Mellerio
J E
JE
Keane
F M
FM
Eady
R A
RA
McGrath
J A
JA
D000954:Antigens, Surface / Q000235:genetics*; D001483:Base Sequence; D016109:Epidermolysis Bullosa, Junctional / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis; D006801:Humans; D007223:Infant; D039161:Integrin alpha6beta4; D016023:Integrins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D011707:Pyloric Stenosis / Q000235:genetics*
D000954:Antigens, Surface; D039161:Integrin alpha6beta4; D016023:Integrins