Novel Mutations Involved in Charcot-Marie-Tooth 4C and Intrafamilial Variability: Let's Not Miss the Forest for the Trees.

Charcot-Marie-Tooth 4C is characterized by early-onset, rapid progression, and mainly associated with SH3TC2 gene mutations. We reported a male patient carrying a novel heterozygous nonsense mutation in SH3TC2 gene along with a heterozygous known pathogenic mutation. Symptoms began at 15 months and by 14 years, he presented significant motor impairment. Both parents exhibited one of the mutations in the heterozygous state, while his 8-year-old brother carried the same compound heterozygosity, showing only a mild phenotype. In our case, we discussed the contribution of compound heterozygosity to intrafamilial variability in Charcot-Marie-Tooth and the role of modifying genes. Thieme. All rights reserved.