Charcot-Marie-Tooth Disease, Axonal, Type 2b1

A number sign (#) is used with this entry because of evidence that Charcot-Marie-Tooth type 2B1 (CMT2B1) is caused by homozygous mutation in the lamin A/C gene (LMNA; 150330) on chromosome 1q22.

Description

Charcot-Marie-Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies. On the basis of electrophysiologic criteria, CMT is divided into 2 major types: type 1, the demyelinating form, characterized by a motor median nerve conduction velocity less than 38 m/s (see CMT1B; 118200); and type 2, the axonal form, with a normal or slightly reduced nerve conduction velocity.

For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A1 (118210).

Clinical Features

Bouhouche et al. (1999) studied a large consanguineous Moroccan autosomal recessive CMT2 family with 9 affected sibs. Onset of CMT was in the second decade in all affected individuals, who had weakness and wasting of the distal lower limb muscles and lower limb areflexia. Pes cavus was present in 7 patients, and there was proximal muscle involvement in 6. Motor nerve conduction velocities were normal or slightly reduced in all patients, reflecting an axonal process.

Mapping

In the large Moroccan family with CMT2, Bouhouche et al. (1999) excluded linkage to known CMT loci. A genomewide search showed linkage of the disorder in this family to markers on 1q, specifically 1q21.2-q21.3.

Molecular Genetics

In 3 consanguineous Algerian families with autosomal recessive CMT2 linked to chromosome 1q21, De Sandre-Giovannoli et al. (2002) identified a homozygous mutation in the LMNA gene (R298C; 150330.0020).

Exclusion Studies

Bouhouche et al. (1999) excluded the myelin protein zero gene (MPZ; 159440) as a candidate for mutation in this disorder by physical mapping and direct sequencing.

Animal Model

De Sandre-Giovannoli et al. (2002) reported that Lmna null mice presented with an axonal clinical and pathologic phenotype that is highly similar to patients with autosomal recessive CMT2.