title: DNA-based prenatal diagnosis of plectin-deficient epidermolysis bullosa simplex associated with pyloric atresia.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Ken
authors.initials: K
authors.lastname: Natsuga
authors.forename: Wataru
authors.initials: W
authors.lastname: Nishie
authors.forename: James R
authors.initials: JR
authors.lastname: McMillan
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawamura
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000032:Abortion, Therapeutic; D000649:Amniocentesis / Q000379:methods*; D001426:Bacterial Proteins; D004476:Ectodermal Dysplasia / Q000235:genetics; D016110:Epidermolysis Bullosa Simplex / Q000235:genetics; D005192:Family Health; D005260:Female; D005315:Fetal Diseases / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D010375:Pedigree; D051190:Plectin / Q000235:genetics*; D011247:Pregnancy
chemical_list: D001426:Bacterial Proteins; C424710:HetF protein, Nostoc punctiforme; C495332:PLEC protein, human; D051190:Plectin