Molecular Genetic Testing

Until recently, there was no reliable molecular diagnostic test for NF1, so diagnosis was limited to application of clinical criteria. Although it is usually easy to establish a clinical diagnosis of NF1, there are several situations in which molecular testing would be useful. The clinical diagnosis often is uncertain in young children with multiple cafe-au-lait spots or an affected parent, because other features such as skin-fold freckles or neurofibromas may not occur until a child is older. Individuals with atypical presentations, such as isolated plexiform neuro-fibromas, may also benefit from molecular testing. Finally, molecular diagnosis offers the possibility of prenatal testing by amniocentesis, chorionic villus sampling, or preimplantation testing.

The major challenges posed in molecular diagnosis are the large size of the gene and the fact that mutations can be distributed anywhere along the gene. There are no major ''hotspots'' or recurrent mutations. Mutation analysis requires use of a set of complementary techniques to detect the various types of mutations, including complete gene deletion, intragenic deletion or duplication, frameshift, stop mutation, splicing mutation, and the rare missense mutation[13] (Table 3). Genotype-phenotype correlations have been difficult to establish. The one clear correlation is that individuals with complete gene deletion tend to have a severe course, with developmental delay, dysmorphic features, and large numbers of neuro-fibromas.[14] The possibility of mosaicism must be considered in those with signs of the disorder in whom no mutation is found; study of affected cells, such as Schwann cells from a neurofibroma, may be necessary to identify a mutation in individuals with mosaicism.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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