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Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Background We have encountered repeated cases of recessive lethal generalized severe (Herlitz-type) junctional epidermolysis bullosa ( JEB gen sev) in infants born to Hungarian Roma parents residing in a small region of Hungary. Objectives To identify the disease-causing mutation and to investigate the genetic background of its unique carrier group. Methods The LAMB3 gene was analysed in peripheral-blood genomic DNA samples, and the pathological consequences of the lethal defect were confirmed by cutaneous LAMB3 cDNA sequencing. A median joining haplotype network within the Y chromosome H1a-M82 haplogroup of individuals from the community was constructed, and LAMB3 single-nucleotide polymorphism ( SNP) patterns were also determined. Results An unconventional intronic splice-site mutation ( LAMB3, c.1133-22G>A) was identified. Thirty of 64 voluntarily screened Roma from the closed community carried the mutation, but none of the 306 Roma from other regions of the country did. The age of the mutation was estimated to be 548 ± 222 years. Within the last year, more patients with JEB gen sev carrying the same unusual mutation have been identified in three unrelated families, all immigrants from the Balkans. Two were compound heterozygous newborns, in Germany and Italy, and one homozygous newborn died in France. Only the French family recognized their Roma background. LAMB3 SNP haplotyping confirmed the link between the apparently unrelated Hungarian, German and Italian male cases, but could not verify the same background in the female newborn from France. Conclusions The estimated age of the mutation corresponds to the time period when Roma were wandering in the Balkans. [ABSTRACT FROM AUTHOR]

Background Tumour-specific expression of matrix metalloproteinase (MMP)-7 has been noted in cutaneous squamous cell carcinomas (SCCs) in patients with recessive dystrophic epidermolysis bullosa (RDEB). Objectives To examine the potential role of MMP-7 in shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in RDEB-associated and sporadic SCCs. Methods Tissue microarrays of RDEB-associated SCC ( n = 20), non-EB SCC ( n = 60) and Bowen disease ( n = 28) were immunostained for MMP-7, CD44 variant 3 (CD44v3) and HB-EGF. Shedding of HB-EGF was studied in vitro using two cutaneous SCC cell lines. Results Immunohistochemical analysis showed that HB-EGF was absent in tumour cells when MMP-7 and CD44v3 colocalized, and that the absence of HB-EGF was more pronounced in RDEB-associated SCCs than in non-EB SCCs. The loss of HB-EGF in MMP-7-CD44v3 double-positive areas was interpreted to indicate shedding and activation of HB-EGF; this was also detected in Bowen disease indicating its importance in the early phase of SCC development. Specific knockdown of MMP-7 expression in human cutaneous SCC cells by small interfering RNA inhibited shedding of HB-EGF and resulted in diminished activation of the EGF receptor (EGFR) and ERK1/2, and in reduced proliferation of SCC cells. Conclusions These findings provide evidence for the role of MMP-7 in promoting the growth of cutaneous SCCs by shedding HB-EGF, and identify EGFR signalling as a potential therapeutic target in RDEB-associated SCC and unresectable sporadic cutaneous SCC. [ABSTRACT FROM AUTHOR]

The article presents a study that determines the conditions and symptoms of palmoplantar keratoderma punctata type 1 (PPKP1). It offers details of the method of the study that observes 13 patients who had typical PPKP1 features. It outlines the result and suggests the importance of long-term maintenance as mandatory to prevent reaggravation.