DNA-based prenatal diagnosis of plectin-deficient epidermolysis bullosa simplex associated with pyloric atresia

Background: Mutations in the plectin gene (PLEC) generally lead to epidermolysis bullosa simplex (EBS) associated with muscular dystrophy. It has been recently demonstrated that PLEC mutations can also cause a different clinical subtype, EBS associated with pyloric atresia (EBS-PA), which shows early lethality. Prenatal diagnosis (PND) of EBS-PA using mutation screening of PLEC has not been described.

Objective: This study aimed to perform DNA-based PND for an EBS-PA family.

Materials and methods: The EBS-PA proband was compound-heterozygous for a paternal c.1350G>A splice-site mutation and a maternal p.Q305X nonsense mutation. Genomic DNA was obtained from amniocytes taken from an at-risk fetus of the proband's family. Direct sequencing and restriction enzyme digestion of polymerase chain reaction products from the genomic DNA were performed.

Results: Mutational analysis showed that the fetus harbored both pathogenic mutations, suggesting that the fetus was a compound-heterozygote and therefore affected with EBS-PA. The skin sample obtained by autopsy from the abortus confirmed the absence of plectin expression at the dermal-epidermal junction.

Conclusions: This is the first successful DNA-based PND for an EBA-PA family.