Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 50

The axonal form of Charcot‐Marie‐Tooth neuropathy (CMT type 2) has autosomal dominant inheritance and is genetically heterogeneous. Only 2 genes are known so far. Two unrelated Caucasian pedigrees (from Russia and Belgium) had 2 distinct mutations in the neurofilament‐light gene (NF‐L)(CMT2E, chromosome 8p21); a single Japanese pedigree had a mutation in the kinesin 1B gene (KIF1B)(CMT2A, chromosome 1p35‐p36). We aimed at investigating the epidemiological relevance of NF‐L in an Italian series with CMT2. The series included 30 index cases with CMT2 diagnosed according to clinical, electrophysiological and pathological criteria, in whom we have ruled out mutations of MPZ/P0 and CX32. In the selected series, the entire coding region of NF‐L was investigated by automated direct nucleotide sequencing. Direct molecular test of the novel identified mutation was performed by analyzing a restriction fragment length polymorphism (RFLP) for AatII. In a single five‐generation pedigree, with 3 affected member examined, we identified a novel heterozygous c.64C > T transition which substitutes a proline with a serine at amino acid residue 22 (Pro22Ser). The mutation appeared to be pathogenic because it co‐segregated with the disease in the pedigree and it was absent in more than 100 healthy controls. The amino acid change occurs in the N‐terminal head domain which regulates the assembly of neurofilaments. The report emphasizes the etiological role of NF‐L in CMT2.