The British journal of dermatology · 2011
Herlitz junctional epidermolysis bullosa: diagnostic features, mutational profile, incidence and population carrier frequency in the Netherlands.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Yuen W Y, Lemmink H H, van Dijk-Bos K K, Sinke R J, Jonkman M F
Аннотация
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).
OBJECTIVES: To present the diagnostic features and molecular analyses of all 22 patients with JEB-H in the Dutch Epidermolysis Bullosa Registry between 1988 and 2011, and to calculate the disease incidence and carrier frequency in the Netherlands.
METHODS: All patients were analysed with immunofluorescence antigen mapping (IF), electron microscopy (EM) and molecular analysis.
RESULTS: The mean lifespan of our patients with JEB-H was 5·8 months (range 0·5-32·6). IF showed absent (91%) or strongly reduced (9%) staining for laminin-332 with monoclonal antibody GB3. In EM the hemidesmosomes and sub-basal dense plates were hypoplastic or absent. We identified mutations in all 22 patients: in 19 we found LAMB3 mutations, in two LAMA3 mutations, and in one LAMC2 mutations. We found three novel splice site mutations in LAMB3: (i) c.29-2A>G resulting in an out-of-frame skip of exon 3 and a premature termination codon (PTC); (ii) c.1289-2_1296del10 leading to an out-of-frame skip of exon 12 and a PTC; and (iii) c.3228+1G>T leading to an exon 21 skip.
CONCLUSIONS: All diagnostic tools should be evaluated to clarify the diagnosis of JEB-H. We have identified 11 different mutations in 22 patients with JEB-H, 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 1 in 249.
OBJECTIVES: To present the diagnostic features and molecular analyses of all 22 patients with JEB-H in the Dutch Epidermolysis Bullosa Registry between 1988 and 2011, and to calculate the disease incidence and carrier frequency in the Netherlands.
METHODS: All patients were analysed with immunofluorescence antigen mapping (IF), electron microscopy (EM) and molecular analysis.
RESULTS: The mean lifespan of our patients with JEB-H was 5·8 months (range 0·5-32·6). IF showed absent (91%) or strongly reduced (9%) staining for laminin-332 with monoclonal antibody GB3. In EM the hemidesmosomes and sub-basal dense plates were hypoplastic or absent. We identified mutations in all 22 patients: in 19 we found LAMB3 mutations, in two LAMA3 mutations, and in one LAMC2 mutations. We found three novel splice site mutations in LAMB3: (i) c.29-2A>G resulting in an out-of-frame skip of exon 3 and a premature termination codon (PTC); (ii) c.1289-2_1296del10 leading to an out-of-frame skip of exon 12 and a PTC; and (iii) c.3228+1G>T leading to an exon 21 skip.
CONCLUSIONS: All diagnostic tools should be evaluated to clarify the diagnosis of JEB-H. We have identified 11 different mutations in 22 patients with JEB-H, 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 1 in 249.