Genetic spectrum and clinical features of PMP22 point mutations in Japanese Charcot-Marie-Tooth disease

*PMP22* point mutations (distinct from duplications/deletions) causing a spectrum of neuropathies

A Japanese multicenter study enrolling 3,352 patients with suspected hereditary peripheral neuropathy compared 30 patients with PMP22 point mutations to 57 patients with PMP22 duplication. Among point mutations, 24 distinct variants were detected, including four novel ones. Compared to duplications, point-mutation carriers had earlier disease onset (0 vs 35 years), less frequent family history (14.3% vs 61.7%), and were less often ambulatory. PMP22 point-mutation-associated neuropathies were characterized by earlier onset and greater severity, illustrating the broad clinical spectrum of PMP22-related disorders.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The distinction between point mutations and duplications/deletions of PMP22 has real prognostic relevance: earlier onset and more severe forms for point mutations. For the clinician, this is a reminder that a normal copy-number dosage does not exclude PMP22 involvement and that the gene must be sequenced. A solid descriptive study in a large cohort, without major mechanistic novelty but useful for counseling.