Challenging the diagnosis of cystic fibrosis in a patient carrying the 186-8T/C allelic variant in the CF transmembrane conductance regulator gene.

Background: This report describe for the first time a clinical case with a CFTR allelic variant 186-8T/C (c.54-8 T/C) in intron 1 of CFTR and underline the importance of applying a combination of genetic and functional tests to establish or exclude a diagnosis of Cystic Fibrosis. In this case the diagnostic algorithm proposed for CF has been successfully applied at our Center and previous CF diagnosis assigned in a different Center was not confirmed.

Impaired CFTR function in mild cystic fibrosis associated with the S977F/T5TG12complex allele in trans with F508del mutation.

Background: The S977F mutation (c.2930C>T) in the CFTR gene (CFTR/ABCC7) is extremely rare. We describe the case of an adult patient carrying the complex allele S977F/T5TG12 in trans with the F508del mutation.

Defective CFTR expression and function are detectable in blood monocytes: development of a new blood test for cystic fibrosis.

Background: Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis of cystic fibrosis (CF) is cumbersome. It is known that leukocytes express detectable levels of CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up and validating a blood test to evaluate CFTR expression and function in leukocytes.

Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton.

The neurofilament light chain (NF-L) is a major constituent of intermediate filaments and plays a pivotal function in the assembly and maintenance of axonal cytoskeleton. Mutations in the NF-L gene (NEFL) cause autosomal dominant neuropathies that are classified either as axonal Charcot-Marie-Tooth (CMT) type 2E (CMT2E) or demyelinating CMT type 1F (CMT1F). The pathophysiological bases of the disorder(s) are elusive.

Gene dosage sensitivity of a novel mutation in the intracellular domain of P0 associated with Charcot-Marie-Tooth disease type 1B.

Autosomal dominant Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by heterozygous mutations in the extracellular domain of P0. Here, we investigated clinically, electrophysiologically and pathologically a pedigree with a novel mutation in the intracellular domain of P0 (P0ic). The mutational analysis included denaturing high performance liquid chromatography (DHPLC) and nucleotide sequencing.

Cellular fate of oligonucleotides when delivered by nanocapsules of poly(isobutylcyanoacrylate).

Dual-labeled phosphorothioate oligonucleotides were encapsulated in the internal aqueous core of poly(isobutylcyanoacrylate) nanocapsules with high yields. Intracellular distribution of naked and encapsulated oligomers was assessed on cultured vascular smooth muscle cells using cell fractionation and confocal microscopy methods. The results showed that cell uptake and more interestingly, nuclear accumulation of oligonucleotides were importantly enhanced when the oligonucleotides were associated to the nanocapsules as compared to the naked oligomers.