Nelis et al. (1998) reported a family with what they described as autosomal dominant 'Charcot-Marie-Tooth disease type 1' (CMT1; see 118200). At age 41 years, the proband had bilateral pes cavus, mild weakness of the peroneal muscles, distal ... Nelis et al. (1998) reported a family with what they described as autosomal dominant 'Charcot-Marie-Tooth disease type 1' (CMT1; see 118200). At age 41 years, the proband had bilateral pes cavus, mild weakness of the peroneal muscles, distal areflexia in the lower limbs, and slowed motor and sensory NCVs (motor median NCV of 34 m/s). Several other family members had decreased NCVs (range, 35 to 42 m/s) without other phenotypic features, whom the authors considered to be 'affected.' After excluding mutations in the coding regions of PMP22 (601097), MPZ (159440), and CX32 (304040), Nelis et al. (1998) identified in the proband a single base change in the promoter region of the PMP22 gene, which did not segregate with the phenotype in this family. De Jonghe et al. (1999) provided further information on the family reported by Nelis et al. (1998). Nerve biopsy of the proband revealed demyelination and remyelination, thin myelin sheaths, and rare onion bulb formations. Twelve relatives with slowed NCV were clinically asymptomatic, but were considered to have hereditary motor and sensory neuropathy I (HMSN I) because of the slowed NCV. However, the authors emphasized that the findings were unusual for HMSN, and concluded that the phenotype in this family was clinically and genetically distinct from known forms of CMT.
In the family with slowed NCV described by Nelis et al. (1998), Verhoeven et al. (2003) identified a heterozygous mutation in the ARHGEF10 gene (608136.0001) that segregated with the phenotype.