CHARCOT-MARIE-TOOTH DISEASE TYPE 1A - MUTATIONAL MECHANISMS AND CANDIDATE GENE

Charcot-Marie-Tooth disease type 1A, the most common inherited peripheral neuropathy, is associated with a submicroscopic DNA duplication of 1.5 Mb that can arise de novo, and which is flanked by a >17 kb mosaic repeat. The PMP22 gene, encoding a peripheral myelin protein, maps within the duplication. In a subset of Charcot-Marie-Tooth patients, point mutations can occur within the gene. Thus, the alternative mechanisms of overexpression of PMP22 and structural alterations in the protein encoded can cause the disease phenotype.