In a previous study, we have shown that N-myc downstream-regulated gene 1 
(NDRG1), classified in databases as a tumor suppressor and heavy metal-response 
protein, is mutated in hereditary motor and sensory neuropathy Lom (HMSNL), a 
severe autosomal recessive form of Charcot-Marie-Tooth (CMT) disease. The 
private founder mutation R148X, causing HMSNL in patients of Romani ethnicity, 
has so far remained the only molecular defect linking NDRG1 to a specific 
disease phenotype. Here we report the first study aiming to assess the overall 
contribution of this gene to the pathogenesis of peripheral neuropathies, in 
cases where the most common causes of CMT disease have been excluded. Sequence 
analysis of NDRG1 in 104 CMT patients of diverse ethnicity identified one novel 
disease-causing mutation, IVS8-1G>A (g.2290787G>A), which affects the 
splice-acceptor site of IVS8 and results in the skipping of exon 9. The 
phenotype of the IVS8-1G>A homozygote was very closely related to that of HMSNL 
patients. In addition, we have detected homozygosity for the known R148X 
mutation in two affected individuals. Mutations in NDRG1 thus accounted for 
2.88% of our overall group of patients, and for 4.68% of cases with 
demyelinating neuropathies. No other variants were identified in the coding 
sequence, whereas 12 single nucleotide polymorphisms were observed in the 
introns. Hum Mutat 22:129-135, 2003.