Herlitz junctional epidermolysis bullosa: diagnostic features, mutational profile, incidence, and population carrier frequency in the Netherlands.

Herlitz junctional epidermolysis bullosa: diagnostic features, mutational profile, incidence, and population carrier frequency in the Netherlands.

Br J Dermatol. 2011 Aug 1;

Authors: Yuen WY, Lemmink HH, van Dijk-Bos KK, Sinke RJ, Jonkman MF

Abstract
Background:  Junctional epidermolysis bullosa, type Herlitz (JEB-H) is a lethal, autosomal recessive blistering disease caused by null mutations in the genes coding for the lamina lucida/densa adhesion protein laminin-332 (LAMB3, LAMA3 and LAMC2). Objective:  To present the diagnostic features and molecular analyses of all 22 JEB-H patients in the Dutch Epidermolysis Bullosa Registry between 1988-2011, and to calculate the disease incidence and carrier frequency in the Netherlands. Methods:  All patients were analyzed with immunofluorescence antigen mapping (IF), electron microscopy (EM), and molecular analysis. Results:  The average lifespan of our JEB-H patients was 5.8 months (range 0.5-32.6 months). IF showed absent (90.9%) or strongly reduced (9.1%) staining for laminin-332 with monoclonal antibody GB3. In EM the hemidesmosomes and subbasal dense plates were hypoplastic or absent. We identified mutations in all 22 patients: in 86.4% we found LAMB3 mutations, in 9.1%LAMA3 mutations, and in 4.5%LAMC2 mutations. We found three novel splice site mutations in LAMB3: (1) c.29-2A>G resulting in an out-of-frame skip of exon 3 and a PTC (2) c.1289-2_1296del10 leading to an out-of-frame skip of exon 12 and a PTC (3) c.3228+1G>T leading to an exon 21 skip. Conclusions:  All diagnostic tools should be evaluated to clarify the diagnosis JEB-H. We have identified eleven different mutations in 22 JEB-H patients, three of them novel. In the Netherlands the incidence rate of JEB-H is 4.0 per one million live births. The carrier frequency of a JEB-H mutation in the Dutch population is one in 249.

PMID: 21801158 [PubMed – as supplied by publisher]

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