A novel LITAF/SIMPLE mutation within a family with a demyelinating form of Charcot–Marie–Tooth disease

•Clinical, electrophysiological, neuropathological findings of a CMT1 family•A novel SIMPLE missense mutation (p.Pro135Arg)•The novel heterozygous missense mutation co-segregates with the disease•The molecular characterization of CMT1 should include the screening of the SIMPLE.

Charcot–Marie–Tooth disease type 1 (CMT1) is a common disorder of the peripheral nervous system. The underlying genetic cause is highly heterogeneous, and mutations in SIMPLE (small integral membrane protein of lysosome/late endosome) represent a rare cause of CMT type 1, named CMT1C. Herein, we report the clinical, electrophysiological, and neuropathological findings of an Italian CMT1 family with a novel SIMPLE missense mutation. The family exhibited electrophysiological signs of demyelination, predominantly affecting the lower limbs, with conduction blocks, and a wide variability of age of onset among the members. Molecular analysis identified the novel heterozygous missense mutation p.Pro135Arg in SIMPLE which co-segregated with the disease within the pedigree. In conclusion, our findings confirm that the genetic analysis of LITAF/SIMPLE should be considered for the diagnostic flow-chart of CMT1 patient, especially when nerve conduction studies show the presence of conduction blocks.