Clinical characterization and genetic analysis of a possible novel type of dominant Charcot-Marie-Tooth disease

A family of dominant Charcot-Marie-Tooth disease with eleven members, six of them symptomatic, was characterized clinically and genetically. The ages at onset ranged from 10 to 45 years, and the clinical severity varied from no symptom to being wheelchair-bound. The median motor nerve conduction velocities ranged from 16.5 to 45.7 m/s. Men were more severely affected. The sural nerve biopsies in two patients featured demyelinating changes. No mutation in PMP22, MPZ, GJB1, NEFL, LITAF, EGR2, MFN2, HSP27, HSP22, GADP1, YARS, and DNM2 genes was found in the proband. Haplotype analyzes excluded linkage to the previously reported dominant CMT loci. A genomewide screen with 400 microsatellite markers and multipoint linkage analyzes revealed that the highest LOD score was around 1.6 on chromosome 3q28-q29, suggestive of a weak but possible linkage at this locus. The results of this study implicate the existence of a novel genetic locus for this syndrome.