ELEVATED EXPRESSION OF MESSENGER-RNA FOR PERIPHERAL MYELIN PROTEIN-22IN BIOPSIED PERIPHERAL-NERVES OF PATIENTS WITH CHARCOT-MARIE-TOOTH-DISEASE TYPE 1A

The human peripheral myelin protein 22 (PMP-22) gene has been mapped t o chromosome 17p11.2 in the duplicated region associated with Charcot- Marie-Tooth disease type IA. Southern blot analysis using PMP-22 as a probe indicated that the PMP-22 gene was duplicated in 5 patients from unrelated Japanese families with Charcot-Marie-Tooth disease type 1. In order to investigate whether or not an extra copy of PMP-22 has an effect on its gene expression, we analyzed relative expression of mess enger RNA for PMP-22 and protein 0 (PO) against beta-actin by Northern blotting in biopsied nerves of the patients with type IA disease, and compared the results with those of patients having other demyelinatin g neuropathies and the autopsied nerves of patients without neuropathi es. The relative expression of PMP-22 messenger RNA in 5 patients with Charcot-Marie-Tooth disease type 1A was significantly higher than tha t in 5 patients with other demyelinating neuropathies (P < 0.05). Ther e was no statistically significant difference in PO expression between them. This study provided direct evidence for elevated expression of PMP-22 in peripheral nerves of patients with Charcot-Marie-Tooth disea se type 1A as the result of a gene dosage effect. However. the relatio n between elevated expression of PMP-22 and the mechanism causing demy elination remains undetermined.