A family with a novel frameshift mutation in the PMP22 gene (c.433_434insC) causing a phenotype of hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies is usually due to PMP22 deletion. Point mutations of PMP22 causing an hereditary neuropathy with liability to pressure palsies phenotype are rare. We describe a clinical and electrodiagnostic phenotype of hereditary neuropathy with liability to pressure palsies in a 21-year-old woman, which led to our detecting a novel frameshift mutation of PMP22. This mutation was also found in her mother and brother and corresponded to an insertion of one cytidine between nucleotides 433 and 434 in the last coding exon (c.433_434insC). The mutated PMP22 protein lacks the last 15 amino acids and has a modified C terminus lengthened to 221 residues instead of 160 (Leu145fsX222). The mother and the proband had a clinical and electrophysiological hereditary neuropathy with liability to pressure palsies phenotype. The brother was asymptomatic, but the results of electrodiagnostic tests were suggestive of hereditary neuropathy with liability to pressure palsies. This observation of a new mutation mostly leading to a PMP22 haploinsufficiency provides further evidence of the diversity of phenotypes associated with frameshift PMP22 mutations.