title: A Japanese-specific recurrent mutation and a novel splice site mutation in the LAMC2 gene identified in two Japanese families with Herlitz junctional epidermolysis bullosa.
abstract: BACKGROUND
  Herlitz junctional epidermolysis bullosa (H-JEB) is an extremely rare genodermatosis characterized by lethality owing to severe blister formation. We report two unrelated Japanese patients with H-JEB. Genetic analyses detected a single nonsense mutation on the LAMC2 gene in these two patients.
  
  
  OBJECTIVE
  To identify the mutation involved and describe the first reported Japanese recurrent mutation in the LAMC2 gene.
  
  
  METHODS
  Direct sequencing was performed of DNA from either peripheral blood or fetal cells in amniotic fluid. Reverse transcriptase PCR was used to confirm that an aberrant transcript resulted from the splice site mutation. A haplotype analysis was performed to define the origin of the recurrent mutation.
  
  
  RESULTS
  Both patients had blisters and erosions on the trunk and limbs at birth, with nail dystrophy. Patient 1 died as a result of sepsis at 30 weeks of age, and patient 2 died as a result of disseminated intravascular coagulation at 20 weeks of age. Mutation analysis of the LAMC2 gene revealed that patient 1 was compound heterozygous for a nonsense mutation (p.Cys553X) and a novel splice site mutation (c.2868+1delG), and patient 2 was a homozygous for p.Cys553X. Prenatal diagnosis performed during a subsequent pregnancy in family 2 revealed that this second child was heterozygous for p.Cys553X, and was thus not affected. Haplotype analysis suggested that a p.Cys553X allele derived from the same origin had been independently inherited by these two unrelated families.
  
  
  CONCLUSIONS
  p.Cys553X in the LAMC2 gene may be a Japanese-specific recurrent mutation as a result of a founder effect, and it may therefore be useful for initial screening in the mutation analysis of H-JEB.
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kouno
authors.forename: R
authors.initials: R
authors.lastname: Ko
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.forename: T
authors.initials: T
authors.lastname: Ouchi
authors.forename: K
authors.initials: K
authors.lastname: Sueoka
authors.forename: T
authors.initials: T
authors.lastname: Masunaga
authors.forename: A
authors.initials: A
authors.lastname: Ishiko
mesh_terms: D044466:Asian People / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics* / Q000503:physiopathology; D017809:Fatal Outcome; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007797:Laminin / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D018389:Codon, Nonsense; C400567:LAMC2 protein, human; D007797:Laminin