• Charcot-Marie-Tooth neuropathy
• CMT2
• axonal CMT
• genetic linkage
• chromosome 12q

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of disorders that involve the peripheral nervous system.¹ It is characterised by progressive distal neurogenic muscular atrophy and weakness that initially affects the peroneal muscles and later the hands. Charcot-Marie-Tooth disease type 1 (CMT1), also called hereditary motor and sensory neuropathy type I (HMSN I), is a dominantly inherited demyelinating neuropathy characterised by reduced nerve conduction velocities (NCV) (motor median NCV <38 m/s). Charcot-Marie-Tooth disease type 2 (CMT) 2, or HMSN II, is a dominantly inherited axonal neuropathy characterised by normal or slightly reduced NCV. Both autosomal dominant CMT1 and autosomal dominant CMT2 are genetically heterogeneous, with five and six loci, respectively.² Most patients with CMT1 have a 1.4 Mb tandem duplication on chromosome 17p11.2 (CMT1A (MIM 118220)).^3,4 Other patients with CMT1 may have point mutations in the peripheral myelin protein 22 gene (PMP22 in CMT1A (MIM 60197)),⁵ myelin protein zero gene (MPZ in CMT1B (MIM 159440)),⁶ lipopolysaccharide induced tumour necrosis factor gene (LITAF in CMT1C (MIM 603795)),⁷ early growth response 2 gene (EGR2 in CMT1D (MIM 129010)),⁸ or the gap junction protein beta 1 gene (GJB1 in CMT1X (MIM 304040)).⁹ Patients with CMT2 may have point mutations in the kinesin family member 1B gene (KIF1B in CMT2A (MIM 605995)),¹⁰ RAB7, member RAS oncogene family (RAB7 in CMT2B (MIM 602298)),¹¹ glycyl tRNA synthetase (GARS in CMT2D (MIM 600287)),¹² or neurofilament light polypeptide (NEFL in CMT2E (MIM 607684)).¹³ The genes for CMT2C and CMT2F have not been identified yet.^14,15 Some patients with CMT2 have also been reported to have specific mutations in the MPZ gene.^16,17