#614228
Table of Contents
Alternative titles; symbols
A number sign (#) is used with this entry because autosomal dominant axonal Charcot-Marie-Tooth disease type 2O (CMT2O) is caused by heterozygous mutation in the DYNC1H1 gene (600112) on chromosome 14q32.
For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Weedon et al. (2011) reported a large 4-generation family with autosomal dominant inheritance of an axonal peripheral neuropathy consistent with CMT. Affected individuals presented in childhood with delayed motor milestones and/or an abnormal gait and difficulty running. Physical examination showed slowly progressive distal lower limb weakness and wasting with pes cavus deformity. Upper limb involvement was less common, and ambulation was usually maintained through adulthood. Nerve conduction studies were within the normal range, and sural nerve biopsies demonstrated changes consistent with axonal degeneration. Some individuals had transient paresthesia and neuropathic lower limb pain. There was significant variability in some other features: reflexes could be lost or preserved, and the degree and modality of distal sensory impairment also varied. Some had learning difficulties.
The transmission pattern of CMT2O in the family reported by Weedon et al. (2011) was consistent with autosomal dominant inheritance.
In affected members of a large 4-generation family with autosomal dominant axonal CMT2O, Weedon et al. (2011) identified a heterozygous mutation in the DYNC1H1 gene (H306R; 600112.0001). The mutation was identified by exome sequencing. Weedon et al. (2011) noted that mouse models had implicated mutations in this gene in neuropathic disease (Hafezparast et al., 2003).
Hafezparast, M., Klocke, R., Ruhrberg, C., Marquardt, A., Ahmad-Annuar, A., Bowen, S., Lalli, G., Witherden, A. S., Hummerich, H., Nicholson, S., Morgan, P. J., Oozageer, R., and 27 others. Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300: 808-812, 2003. [PubMed: 12730604, related citations] [Full Text]
Weedon, M. N., Hastings, R., Caswell, R., Xie, W., Paszkiewicz, K., Antoniadi, T., Williams, M., King, C., Greenhalgh, L., Newbury-Ecob, R., Ellard, S. Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease. Am. J. Hum. Genet. 89: 308-312, 2011. [PubMed: 21820100, images, related citations] [Full Text]
Alternative titles; symbols
SNOMEDCT: 782829002; ORPHA: 284232; DO: 0110175;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 14q32.31 | Charcot-Marie-Tooth disease, axonal, type 2O | 614228 | Autosomal dominant | 3 | DYNC1H1 | 600112 |
A number sign (#) is used with this entry because autosomal dominant axonal Charcot-Marie-Tooth disease type 2O (CMT2O) is caused by heterozygous mutation in the DYNC1H1 gene (600112) on chromosome 14q32.
For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Weedon et al. (2011) reported a large 4-generation family with autosomal dominant inheritance of an axonal peripheral neuropathy consistent with CMT. Affected individuals presented in childhood with delayed motor milestones and/or an abnormal gait and difficulty running. Physical examination showed slowly progressive distal lower limb weakness and wasting with pes cavus deformity. Upper limb involvement was less common, and ambulation was usually maintained through adulthood. Nerve conduction studies were within the normal range, and sural nerve biopsies demonstrated changes consistent with axonal degeneration. Some individuals had transient paresthesia and neuropathic lower limb pain. There was significant variability in some other features: reflexes could be lost or preserved, and the degree and modality of distal sensory impairment also varied. Some had learning difficulties.
The transmission pattern of CMT2O in the family reported by Weedon et al. (2011) was consistent with autosomal dominant inheritance.
In affected members of a large 4-generation family with autosomal dominant axonal CMT2O, Weedon et al. (2011) identified a heterozygous mutation in the DYNC1H1 gene (H306R; 600112.0001). The mutation was identified by exome sequencing. Weedon et al. (2011) noted that mouse models had implicated mutations in this gene in neuropathic disease (Hafezparast et al., 2003).
Hafezparast, M., Klocke, R., Ruhrberg, C., Marquardt, A., Ahmad-Annuar, A., Bowen, S., Lalli, G., Witherden, A. S., Hummerich, H., Nicholson, S., Morgan, P. J., Oozageer, R., and 27 others. Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300: 808-812, 2003. [PubMed: 12730604] [Full Text: https://doi.org/10.1126/science.1083129]
Weedon, M. N., Hastings, R., Caswell, R., Xie, W., Paszkiewicz, K., Antoniadi, T., Williams, M., King, C., Greenhalgh, L., Newbury-Ecob, R., Ellard, S. Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease. Am. J. Hum. Genet. 89: 308-312, 2011. [PubMed: 21820100] [Full Text: https://doi.org/10.1016/j.ajhg.2011.07.002]
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