Alternative titles; symbols
ORPHA: 139589; DO: 0111202;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2p13.1 | Neuronopathy, distal hereditary motor, autosomal dominant 14 | 607641 | Autosomal dominant | 3 | DCTN1 | 601143 |
A number sign (#) is used with this entry because of evidence that autosomal dominant distal hereditary motor neuronopathy-14 (HMND14) is caused by heterozygous mutation in the DCTN1 gene (601143) on chromosome 2p13.
For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant distal HMN, see HMND1 (182960).
Puls et al. (2003) identified a family with a slowly progressive, autosomal dominant form of motor neuron disease without sensory symptoms. Onset of the disorder was in early adulthood with breathing difficulty due to vocal fold paralysis, progressive facial weakness, and weakness and muscle atrophy in the hands. Weakness and muscle atrophy in the distal lower extremities developed later.
There is some phenotypic overlap between this disorder and amyotrophic lateral sclerosis (ALS; 105400).
The transmission pattern of HMND14 in the family reported by Puls et al. (2003) was consistent with autosomal dominant inheritance.
Puls et al. (2003) performed a genomewide screen in their family with lower motor neuron disease and demonstrated linkage to 2p13 with a maximum lod score of 4.05 at D2S2109 at recombination fraction theta = 0.0. Multipoint linkage analysis gave a maximum lod score of 5.6.
Puls et al. (2003) found a gly59-to-ser mutation in the DCTN1 gene (G59S; 601143.0001) in all affected individuals of the family they studied with lower motor neuron disease.
Among 250 patients with a putative diagnosis of amyotrophic lateral sclerosis, Munch et al. (2004) identified a woman with a mutation in the DCTN1 gene (T1249I; 601143.0002). She had onset at age 56 years of distal lower limb weakness and atrophy without involvement of the upper limbs or bulbar muscles. Munch et al. (2004) considered the phenotype in this patient to be different from that reported by Puls et al. (2003); they stated that 'one of the main differences' was 'the lack of upper motor neuron signs in patients with the G59S mutation,' but specific clinical details were lacking.
Munch, C., Sedlmeier, R., Meyer, T., Homberg, V., Sperfeld, A. D., Kurt, A., Prudlo, J., Peraus, G., Hanemann, C. O., Stumm, G., Ludolph, A. C. Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology 63: 724-726, 2004. [PubMed: 15326253] [Full Text: https://doi.org/10.1212/01.wnl.0000134608.83927.b1]
Puls, I., Jonnakuty, C., LaMonte, B. H., Holzbaur, E. L. F., Tokito, M., Mann, E., Floeter, M. K., Bidus, K., Drayna, D., Oh, S. J., Brown, R. H., Jr., Ludlow, C. L., Fischbeck, K. H. Mutant dynactin in motor neuron disease. Nature Genet. 33: 455-456, 2003. [PubMed: 12627231] [Full Text: https://doi.org/10.1038/ng1123]