#605588
Table of Contents
Alternative titles; symbols
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.
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).
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.
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.
The transmission pattern of CMT2B1 in the families reported by Bouhouche et al. (1999) was consistent with autosomal recessive inheritance.
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.
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.
Bouhouche, A., Benomar, A., Birouk, N., Mularoni, A., Meggouh, F., Tassin, J., Grid, D., Vandenberghe, A., Yahyaoui, M., Chkili, T., Brice, A., LeGuern, E. A locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 1q21.2-q21.3. Am. J. Hum. Genet. 65: 722-727, 1999. [PubMed: 10441578, related citations] [Full Text]
De Sandre-Giovannoli, A., Chaouch, M., Kozlov, S., Vallat, J.-M., Tazir, M., Kassouri, N., Szepetowski, P., Hammadouche, T., Vandenberghe, A., Stewart, C. L., Grid, D., Levy, N. Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse. Am. J. Hum. Genet. 70: 726-736, 2002. Note: Erratum: Am. J. Hum. Genet. 70: 1075 only, 2002. [PubMed: 11799477, images, related citations] [Full Text]
Alternative titles; symbols
SNOMEDCT: 725048002; ORPHA: 98856; DO: 0110156;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q22 | Charcot-Marie-Tooth disease, type 2B1 | 605588 | Autosomal recessive | 3 | LMNA | 150330 |
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.
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).
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.
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.
The transmission pattern of CMT2B1 in the families reported by Bouhouche et al. (1999) was consistent with autosomal recessive inheritance.
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.
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.
Bouhouche, A., Benomar, A., Birouk, N., Mularoni, A., Meggouh, F., Tassin, J., Grid, D., Vandenberghe, A., Yahyaoui, M., Chkili, T., Brice, A., LeGuern, E. A locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 1q21.2-q21.3. Am. J. Hum. Genet. 65: 722-727, 1999. [PubMed: 10441578] [Full Text: https://doi.org/10.1086/302542]
De Sandre-Giovannoli, A., Chaouch, M., Kozlov, S., Vallat, J.-M., Tazir, M., Kassouri, N., Szepetowski, P., Hammadouche, T., Vandenberghe, A., Stewart, C. L., Grid, D., Levy, N. Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse. Am. J. Hum. Genet. 70: 726-736, 2002. Note: Erratum: Am. J. Hum. Genet. 70: 1075 only, 2002. [PubMed: 11799477] [Full Text: https://doi.org/10.1086/339274]
Dear OMIM User,
To ensure long-term funding for the OMIM project, we have diversified our revenue stream. We are determined to keep this website freely accessible. Unfortunately, it is not free to produce. Expert curators review the literature and organize it to facilitate your work. Over 90% of the OMIM's operating expenses go to salary support for MD and PhD science writers and biocurators. Please join your colleagues by making a donation now and again in the future. Donations are an important component of our efforts to ensure long-term funding to provide you the information that you need at your fingertips.
Thank you in advance for your generous support,
Ada Hamosh, MD, MPH
Scientific Director, OMIM