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 .

Diseases
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Diseases presenting "prenatal diagnosis" symptom

22q11.2 deletion syndrome

achondroplasia

adrenomyeloneuropathy

alexander disease

alpha-thalassemia

aromatase deficiency

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

classical phenylketonuria

cohen syndrome

congenital adrenal hyperplasia

congenital diaphragmatic hernia

congenital toxoplasmosis

cystinuria

dentinogenesis imperfecta

epidermolysis bullosa simplex

harlequin ichthyosis

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

junctional epidermolysis bullosa

kindler syndrome

krabbe disease

lamellar ichthyosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

monosomy 21

neonatal adrenoleukodystrophy

oculocutaneous albinism

omenn syndrome

phenylketonuria

primary hyperoxaluria type 1

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

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