Pachyonychia congenita cornered: report on the 11th A nnual I nternational P achyonychia C ongenita C onsortium Meeting

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109650/1/bjd13341.pd

Report of the 13th Annual International Pachyonychia Congenita Consortium Symposium

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137611/1/bjd15417.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137611/2/bjd15417_am.pd

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

LIMITS ON NEUTRINO OSCILLATIONS FROM MUON-DECAY NEUTRINOS

No evidence for neutrino oscillations is seen in our experiment which observed neutrinos from muon-decays at rest. Upper limits on oscillation parameters are presented for neutrino mixing of the kind {nu}{sub e}{leftrightarrow}{nu}{sub {mu}} and also of the kind {nu}{sub e}{leftrightarrow}{nu}{sub i}, i{ne}{mu}