SEVERE CHARCOT-MARIE-TOOTH DISEASE AND RELATED HEREDITARY NEUROPATHIES: AN ITALIAN COLLABORATIVE NETWORK FOR IMPLEMENTING THE MOLECULAR ANALYSIS OF RARE FORMS AND NEW GENES

Charcot-Marie-Tooth disease (CMT) includes clinical and genetic heterogeneous hereditary motor and sensory neuropathies and represents the most common inherited disorder of the neuromuscular system. In current practice, more severe forms with onset in childhood remain still orphan of a definite molecular genetic diagnosis. For those forms there are now new candidate genes whose roles must be fully elucidated. The involved genes are numerous and disclose a complex organization making their analysis very difficult, time-consuming and expensive. The present multicentre project is aimed at implementing the molecular diagnosis of rare neglected (orphan) forms of CMT, making it available on a national scale. The genes to be analysed are: LITAF, EGR2, NFL, GDAP1, MTMR2, SBF2, KIAA1985, NDRG1, PRX, MFN2, LMNA, HSPB1, HSPB8. The research units will exploit a new powerful high-efficiency technology, called DHPLC (Denaturing High-Performance Liquid Chromatography); they will investigate a large series of uncharacterized cases of CMT, trying to provide them with a definite molecular diagnosis. The research unit will also provide neurologists and neuropediatricians with a rational clinical, genetic and molecular diagnostic flow chart. The goals of the project are to improve the genetic counselling of patients and their families and to avoid their current odyssey through fruitless instrumental investigations.