Variants in the genes DCTN 2 , DNAH 10 , LRIG 3, and MYO 1A are associated with intermediate Charcot–Marie–Tooth disease in a Norwegian family

Charcot–Marie–Tooth disease ( CMT ) is a heterogeneous inherited neuropathy. The number of known CMT genes is rapidly increasing mainly due to next‐generation sequencing technology, at present more than 70 CMT ‐associated genes are known. We investigated whether variants in the DCTN 2 could cause CMT . Material and methods Fifty‐nine Norwegian CMT families from the general population with unknown genotype were tested by targeted next‐generation sequencing ( NGS ) for variants in DCTN 2 along with 32 CMT genes and 19 other genes causing other inherited neuropathies or neuronopathies, due to phenotypic overlap. In the family with the DCTN 2 variant, exome sequencing was then carried out on all available eight family members to rule out the presence of more potential variants. Results Targeted NGS identified in one family a variant of DCTN 2 , c.337C>T, segregating with the phenotype in five affected members, while it was not present in the three unaffected members. The DCTN 2 variant c.337C>T; p.(His113Tyr) was neither found in in‐house controls nor in SNP databases. Exome sequencing revealed a singular heterozygous shared haplotype containing four genes, DCTN 2 , DNAH 10 , LRIG 3, and MYO 1A , with novel sequence variants. The haplotype was shared by all the affected members, while the unaffected members did not have it. Conclusions This is the first time a haplotype on chromosome 12 containing sequence variants in the genes DCTN 2 , DNAH 10 , LRIG 3, and MYO 1A has been linked to an inherited neuropathy in humans.