Denaturing high-performance liquid chromatography of the myotubularin-related 2 gene (MTMR2) in unrelated patients with Charcot-Marie-Tooth disease suggests a low frequency of mutation in inherited neuropathy.

Charcot-Marie-Tooth type 4B (CMT4B), an autosomal recessive demyelinating neuropathy characterized by focally folded myelin sheaths in the peripheral nerve, has been associated with mutations in the gene encoding myotubularin-related protein 2, MTMR2, on chromosome 11q22. To investigate whether mutations in MTMR2 may also cause different forms of CMT, we screened 183 unrelated patients with a broad spectrum of CMT and related neuropathies using denaturing high-performance liquid chromatography. We identified four frequent and three rare exonic variants; two of the rare variants were identified in two unrelated patients with congenital hypomyelinating neuropathy and not in the normal controls. Our results suggest that loss-of-function mutations in MTMR2 are preferentially associated with the CMT4B phenotype.