A novel keratin 13 variant in a four-generation family with white sponge nevus

Dermatology-oncolog

Electrophoretic and immunological analysis of proteins in the muscular dystrophies

SIGLEAvailable from British Library Document Supply Centre- DSC:DXN1662 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

SiRNA-mediated selective inhibition of mutant keratin mRNAs responsible for the skin disorder pachyonychia congenita

RNA interference offers a novel approach for treating genetic disorders including the rare monogenic skin disorder pachyonychia congenita (PC). PC is caused by mutations in keratin 6a (K6a), K6b, K16, and K17 genes, including small deletions and single nucleotide changes. Transfection experiments of a fusion gene consisting of K6a and a yellow fluorescent reporter (YFP) resulted in normal keratin filament formation in transfected cells as assayed by fluorescence microscopy. Similar constructs containing a single nucleotide change (N171K) or a three-nucleotide deletion (N171del) showed keratin aggregate formation. Mutant-specific small inhibitory RNAs (siRNAs) effectively targeted these sites. These studies suggest that siRNAs can discriminate single nucleotide mutations and further suggest that "designer siRNAs" may allow effective treatment of a host of genetic disorders including PC

Filaggrine genmutaties in de Nederlandse populatie

FLG mutations R501X, 2282del4, and R2447X were genotyped in the PIAMA birth cohort (n=934) to evaluate longitudinally their association with eczema, specific IgE sensitization, asthma combined with bronchial hyperresponsiveness and hay fever up to 8 years of age and their interaction with cat exposure. Combined FLG mutations were significantly associated with eczema at all ages that started in the first year. The association between the major 2282del4 variant and eczema up to age 8 was stronger in children with a cat at home (OR=6,0; 95% CI, 3,2-11,3). A significant association between 2282del4 and sensitization (specific IgE ≥0.70 kU/L) was only found in children with early-life cat exposure (OR=5,4; 95% CI, 1,2-23,6). The distribution of FLG variants was not significantly different between atopic and nonatopic eczema and both were significantly associated with the combined genotype. The prevalence of asthma at 0 to 8 years combined with bronchial hyperresponsiveness at 8 years was significantly associated with the combined genotype (OR=3,7; 95% CI, 1,8-7,5). Hay fever was significantly associated with 2282del4 from age 5 onwards (OR=3,9; 95% CI, 1,5-10,5). In conclusion, analyses of the longitudinal data showed that eczema in the first year is a primer determinant of an association between FLG variants and later development of asthma, and hay fever. The 2282del4 variant was significantly associated with sensitization only in children with early-life cat exposure. There likely are two subgroups of children with early onset eczema and FLG mutations: one group that walks an atopic march that starts in the skin, and one group that does not walk the march to allergy

Novel proline substitution mutations in keratin 16 in two cases of pachyonycia congenita type 1.

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