Netherton syndrome (OMIM #256500) is a rare but severe autosomal recessive form of ichthyosis that affects the skin, hair, and immune system. The identification of SPINK5, which encodes for the serine protease inhibitor LEKTI, as the gene responsible for Netherton syndrome, enabled the search for causative mutations in Netherton syndrome patients and families. However, information regarding these mutations and their association with the pathological Netherton syndrome phenotype is scarce. Herein, we provide an up-to-date overview of 80 different mutations in exonic as well as intronic regions that have been currently identified in 172 homozygous or compound heterozygous patients from 144 families. Genotypes with mutations located more upstream in LEKTI correlate with more severe phenotypes compared with similar mutations located towards the 3' region. Furthermore, splicing mutations and post-transcriptional mechanism of nonsense-mediated mRNA decay affect LEKTI expression in variable ways. Genotype-phenotype correlations form the basis of prenatal diagnosis in families with a history of Netherton syndrome and when consanguinity is implied.
clusion:The study supported the hypothesis that leptin and resistin concentrations are higher and adiponectin concentrations are lower in patients with psoriasis compared to controls. Hereby, the suggested pathogenic link between psoriasis and metabolic syndrome/obesity is reinforced and the role of comorbidities in psoriasis is highlighted.
A case-control study was performed to assess the serum levels of TNF-α, IL-12/23p40, and IL-17 in patients with plaque psoriasis, compare them with healthy controls, and correlate them with disease severity, as represented by Psoriasis Area Severity Index (PASI). 32 consecutively selected, untreated patients with active, chronic plaque psoriasis were recruited and compared to 32 age- and sex-matched healthy controls. Serum cytokine levels were determined by solid phase sandwich enzyme linked immunosorbent assay (R&D Systems Europe, Ltd.). The mean serum levels of TNF-α were significantly higher in psoriatic patients compared to those of controls (Mann-Whitney U test; P = 0.000). However, the median serum levels of neither IL-12/23p40 nor IL-17 differ significantly between the 2 groups (Mann-Whitney U test; P = 0.968 and P = 0.311, resp.). No significant correlations were found between PASI and any of the cytokine serum levels (Spearman's rank test; P > 0.05). Despite the well-evidenced therapeutic efficacy of biologic agents targeting TNF-α, IL-12/23p40, and IL-17, serum levels of TNF-α, IL-12/23p40, and IL-17 do not seem to correlate with the severity of psoriatic skin disease in untreated patients, as represented by PASI. Further investigation may add more data on the pathogenetic cascade of psoriasis.
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