A founder effect of c.1938delC in ITGB4 underlies junctional epidermolysis bullosa and its application for prenatal testing.

[junctional epidermolysis bullosa]

Junctional epidermolysis bullosa associated with pyloric atresia (JEB-PA ) is one of the most severe inherited skin diseases , characterized by generalized blister formation and occlusion of the pylorus at birth . Most JEB-PA patients have mutations in the gene encoding β 4 integrin (ITGB 4 ). No recurrent mutations in ITGB 4 have been described as having founder effects . We collected three JEB-PA families with c .1938 delC in ITGB 4 . Haplotype analysis using single nucleotide polymorphism markers throughout ITGB 4 suggested one rare haplotype (2 .8 % of the Han Chinese and ethnic Japanese populations ) in all alleles with c .1938 delC . The parents of one of the three families sought prenatal diagnosis for a subsequent pregnancy . We succeeded in performing prenatal exclusion of JEB-PA using the foetal genomic DNA . Our study clearly demonstrated that recurrent c .1938 delC in ITGB 4 is a founder mutation in JEB-PA patients , and that genotyping of the mutation can be utilized for prenatal diagnosis of JEB-PA .