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.

[junctional epidermolysis bullosa]

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 LAMC 2 gene in these two patients .To identify the mutation involved and describe the first reported Japanese recurrent mutation in the LAMC 2 gene .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 .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 LAMC 2 gene revealed that patient 1 was compound heterozygous for a nonsense mutation (p .Cys 553 X ) and a novel splice site mutation (c .2868 +1 delG ), and patient 2 was a homozygous for p .Cys 553 X . Prenatal diagnosis performed during a subsequent pregnancy in family 2 revealed that this second child was heterozygous for p .Cys 553 X , and was thus not affected . Haplotype analysis suggested that a p .Cys 553 X allele derived from the same origin had been independently inherited by these two unrelated families .p .Cys 553 X in the LAMC 2 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 .