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Charcot-Marie-Tooth (CMT) disease is the most prevalent inherited neuropathy. Today more than 40 CMT genes have been identified. Diagnosing heterogeneous diseases by conventional Sanger sequencing is time consuming and expensive. Thus, more efficient and less costly methods are needed in clinical diagnostics. We included a population based sample of 81 CMT families. Gene mutations had previously been identified in 22 families; the remaining 59 families were analysed by next-generation sequencing. Thirty-two CMT genes and 19 genes causing other inherited neuropathies were included in a custom panel. Variants were classified into five pathogenicity classes by genotype-phenotype correlations and bioinformatics tools. Gene mutations, classified certainly or likely pathogenic, were identified in 37 (46%) of the 81 families. Point mutations in known CMT genes were identified in 21 families (26%), whereas four families (5%) had point mutations in other neuropathy genes,ARHGEF10, POLG, SETX,andSOD1. Eleven families (14%) carried thePMP22duplication and one family carried aMPZduplication (1%). Most mutations were identified not only in known CMT genes but also in other neuropathy genes, emphasising that genetic analysis should not be restricted to CMT genes only. Next-generation sequencing is a cost-effective tool in diagnosis of CMT improving diagnostic precision and time efficiency.

In Table 4 and Supplemental Table 1 of the published paper entitled “Genetic Diagnosis of Charcot-Marie-Tooth Disease in a Population by Next-Generation Sequencing” [1], we classified two variants as likely pathogenic. These two variants ({"type":"entrez-nucleotide","attrs":{"text":"NM_001126131.1","term_id":"187171276","term_text":"NM_001126131.1"}}NM_001126131.1:c.[1491G>C(;)2243G>C]), identified in the POLG gene, were carried by one patient (ID 62). As it was not possible to examine whether the two variants were in cis or trans, that is, situated on the same or different alleles, these two variants should have been reported as uncertain pathogenic variants. This change also influences the Results, where the prevalence of identified variants is corrected to 8 likely and 17 uncertain pathogenic variants. In Figure 1, the number of families with likely pathogenic variants is reduced to n = 7 (9%) and the number for families with uncertain pathogenic variants is increased to n = 10 (12%). And in Figure 2(b), the number of CMT2 families in the category “other point mutations” is reduced to n = 7 (21%) and the number of families with uncertain pathogenic variants is increased to n = 5 (15%). See corrected Figures ​Figures11 and 2(b). Figure 1 Identified variants in 81 Norwegian CMT families from the general population. Our previous studies identified copy-number variations in 12 CMT families and pathogenic point mutations in 10 CMT families [2, 14, 19]. The remaining 59 CMT families were investigated ... Figure 2 Frequencies of certain and likely pathogenic variants in CMT1 and CMT2 families from the Norwegian general population.