Charcot-Marie-Tooth caused by a copy number variation in myelin protein zero

IntroductionCharcot-Marie-Tooth disease (CMT) is the most common inherited disorder of the peripheral nervous system. The majority has a duplication of the peripheral myelin protein 22. CMT is otherwise caused by point mutations or small insertions/deletions in one of the 44 known CMT genes.Methods and ResultsConventional sequencing of six CMT genes were followed by Multiplex Ligation-dependent Probe Amplification (MLPA), array Comparative Genomic Hybridization (aCGH) and breakpoint analysis in a large Norwegian CMT pedigree. Affected had an extra copy of the myelin protein zero (MPZ) gene.ConclusionTo our knowledge this is the first non-peripheral myelin protein 22 copy number variation to cause Charcot-Marie-Tooth disease.

► Charcot-Marie-Tooth disease (CMT) is caused by CNVs or point mutations.
► Duplication of PMP22 has been the only known CNV to cause CMT.
► This study identified a duplication of MPZ in a family with CMT.
► The duplication was observed only in affected members of the family.
► The findings were confirmed by MLPA, aCGH and breakpoint analysis.