Novel 95G>A (R32K) somatic mosaic connexin 32 mutation.

Charcot-Marie-Tooth disease (CMT) is among the most common inherited disorders of the peripheral nervous system, and it is broadly categorized as demyelinating type 1 or axonal type 2 based on nerve conduction studies. Mutations in discrete genes usually segregate into a single phenotype. However, mutations in connexin 32 (Cx32) can produce both axonal and demyelinating CMT phenotypes. Although over 300 mutations have been described in Cx32, somatic mosaicism has only been reported once previously. We report a 39-year-old man who was referred for electrodiagnostic evaluation due to a history of bilateral carpal tunnel syndrome. His physical examination and electrodiagnostic findings demonstrated a mild sensorimotor axonal peripheral neuropathy. Sequencing of his Cx32 (GJB1) gene identified a guanine-to-adenine (G>A) transition at nucleotide position 95. This transition mutation involved approximately one-third of leukocyte-derived genomic DNA. This is the second reported case of somatic mosaicism, and it highlights the phenotypic diversity among CMTX patients.

Subcellular localization of protein kinase C delta and epsilon affects transcriptional and post-transcriptional processes in four-cell mouse embryos.

During mouse preimplantation development, two isozymes of protein kinase C (PKC), delta and epsilon, transiently localize to nuclei at the early four-cell stage. In order to study their functions at this stage, we altered the subcellular localization of these isozymes (ratio of nuclear to cytoplasmic concentrations) with peptides that specifically activate or inhibit translocation of each isozyme. The effects of altering nuclear concentration of each isozyme on transcription (5-bromouridine 5'-triphosphate (BrUTP) incorporation), amount and distribution of small nuclear ribonucleoproteins (snRNPs), nucleolar dynamics (immunocytochemistry for Smith antigen (Sm) protein) and the activity of embryonic alkaline phosphatase (EAP; histochemistry) were examined. We found that nuclear concentration of PKC epsilon correlated with total mRNA transcription. Higher nuclear concentrations of both PKC delta and epsilon decreased storage of snRNPs in Cajal bodies and decreased the number of nucleoli, but did not affect the nucleoplasmic concentration of snRNPs. Inhibiting translocation of PKC delta out of the nucleus at the early four-cell stage decreased cytoplasmic EAP activity, whereas inhibiting translocation of PKC epsilon increased EAP activity slightly. These results indicate that translocation of PKC delta and epsilon in and out of nuclei at the early four-cell stage in mice can affect transcription or message processing, and that sequestration of these PKC in nuclei can also affect the activity of a cytoplasmic protein (EAP).