Distal hereditary motor neuropathy type 7B with Dynactin 1 mutation

Hwang,Sun Hee; Kim,Eun Ja; Hong,Young Bin; Joo,Jaesoon; Kim,Sung Min; Nam,Soo Hyun; Hong,Hyun Dae; Kim,Seung Hyun; Oh,Kiwook; Lim,Jeong‑Geun; Cho,Jeong Hee; Chung,Ki Wha; Choi,Byung‑Ok

doi:10.3892/mmr.2016.5664

Distal hereditary motor neuropathy type 7B with Dynactin 1 mutation

Authors:
- Sun Hee Hwang
- Eun Ja Kim
- Young Bin Hong
- Jaesoon Joo
- Sung Min Kim
- Soo Hyun Nam
- Hyun Dae Hong
- Seung Hyun Kim
- Kiwook Oh
- Jeong‑Geun Lim
- Jeong Hee Cho
- Ki Wha Chung
- Byung‑Ok Choi
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Affiliations: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea, Stem Cell & Regenerative Medicine Center, Samsung Medical Center, Seoul 06351, Republic of Korea, Department of Biological Sciences, Kongju National University, Gongju, South Chungcheong 32588, Republic of Korea, Department of Neurology, Hanyang University College of Medicine, Seoul 04763, Republic of Korea, Department of Neurology, Keimyung University College of Medicine, Daegu 42403, Republic of Korea, Department of Neurology, National Health Insurance Corporation Ilsan Hospital, Goyang, Gyeonggi 10444, Republic of Korea
Published online on: August 22, 2016 https://doi.org/10.3892/mmr.2016.5664
Pages: 3362-3368

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Abstract

Mutations in the Dynactin 1 (DCTN1) gene have been demonstrated to result in various neurodegenerative diseases, including distal hereditary motor neuropathy type 7B (dHMN7B), Perry syndrome, amyotrophic lateral sclerosis and amyotrophic lateral sclerosis‑frontotemporal dementia. However, since the first dHMN7B patient with a DCTN1 mutation was described in 2003, to the best of our knowledge no further cases have been reported. In the present study, the DCTN1 p.G59S mutation was identified in two unrelated families from a total of 24 Korean families with dHMN, by whole exome sequencing. Codon 59 appears to be the mutational hot spot in the DCTN1 gene, as all described dHMN7B patients to date have harbored an identical p.G59S mutation. The families of the present study with the DCTN1 mutation had a milder disease with a later onset compared with the previously described patients. No affected family members exhibited facial muscle weakness or bulbar involvement. One family member demonstrated vocal cord palsy as the initial sign of disease; however, in the other family hand muscle weakness was the first major symptom. No affected patients demonstrated sensory loss or upper motor neuron involvements. Although this is only the second report of dHMN7B resulting from a DCTN1 mutation, the frequency of the DCTN1 mutation was not low in the Korean population examined, and clinical heterogeneities were observed in patients with the DCTN1 mutation. Therefore, it may be beneficial to screen all dHMN patients for the DCTN1 mutation.

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1	Rossor AM, Kalmar B, Greensmith L and Reilly MM: The distal hereditary motor neuropathies. J Neurol Neurosurg Psychiatry. 83:6–14. 2012. View Article : Google Scholar
2	Puls I, Oh SJ, Sumner CJ, Wallace KE, Floeter MK, Mann EA, Kennedy WR, Wendelschafer-Crabb G, Vortmeyer A, Powers R, et al: Distal spinal and bulbar muscular atrophy caused by dynactin mutation. Ann Neurol. 57:687–694. 2005. View Article : Google Scholar : PubMed/NCBI
3	2nd Workshop of the European CMT Consortium: 53rd ENMC International Workshop on Classification and Diagnostic Guidelines for Charcot-Marie-Tooth Type 2 (CMT2-HMSN II) and Distal Hereditary Motor Neuropathy (distal HMN-Spinal CMT) 26–28 September 1997, Naarden, The Netherlands. Neuromuscul Disord. 8:426–431. 1998. View Article : Google Scholar
4	Harding AE and Thomas PK: Genetic aspects of hereditary motor and sensory neuropathy (types I and II). J Med Genet. 17:329–336. 1980. View Article : Google Scholar : PubMed/NCBI
5	Puls I, Jonnakuty C, LaMonte BH, Holzbaur EL, Tokito M, Mann E, Floeter MK, Bidus K, Drayna D, Oh SJ, et al: Mutant dynactin in motor neuron disease. Nat Genet. 33:455–456. 2003. View Article : Google Scholar : PubMed/NCBI
6	Münch C, Sedlmeier R, Meyer T, Homberg V, Sperfeld AD, Kurt A, Prudlo J, Peraus G, Hanemann CO, Stumm G and Ludolph AC: Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology. 63:724–726. 2004. View Article : Google Scholar : PubMed/NCBI
7	Münch C, Rosenbohm A, Sperfeld AD, Uttner I, Reske S, Krause BJ, Sedlmeier R, Meyer T, Hanemann CO, Stumm G and Ludolph AC: Heterozygous R1101K mutation of the DCTN1 gene in a family with ALS and FTD. Ann Neurol. 58:777–780. 2005. View Article : Google Scholar : PubMed/NCBI
8	Farrer MJ, Hulihan MM, Kachergus JM, Dächsel JC, Stoessl AJ, Grantier LL, Calne S, Calne DB, Lechevalier B, Chapon F, et al: DCTN1 mutations in Perry syndrome. Nat Genet. 41:163–165. 2009. View Article : Google Scholar : PubMed/NCBI
9	Irobi J, Dierick I, Jordanova A, Claeys KG, De Jonghe P and Timmerman V: Unraveling the genetics of distal hereditary motor neuronopathies. Neuromolecular Med. 8:131–146. 2006. View Article : Google Scholar : PubMed/NCBI
10	Holzbaur EL and Vallee RB: DYNEINS: Molecular structure and cellular function. Annu Rev Cell Biol. 10:339–372. 1994. View Article : Google Scholar : PubMed/NCBI
11	Irobi J, De Jonghe P and Timmerman V: Molecular genetics of distal hereditary motor neuropathies. Hum Mol Genet. 13:R195–R202. 2004. View Article : Google Scholar : PubMed/NCBI
12	Moore JK, Sept D and Cooper JA: Neurodegeneration mutations in dynactin impair dynein-dependent nuclear migration. Proc Natl Acad Sci USA. 106:5147–5152. 2009. View Article : Google Scholar : PubMed/NCBI
13	Levy JR, Sumner CJ, Caviston JP, Tokito MK, Ranganathan S, Ligon LA, Wallace KE, LaMonte BH, Harmison GG, Puls I, et al: A motor neuron disease-associated mutation in p150Glued perturbs dynactin function and induces protein aggregation. J Cell Biol. 172:733–745. 2006. View Article : Google Scholar : PubMed/NCBI
14	Vaughan KT and Vallee RB: Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued. J Cell Biol. 131:1507–1516. 1995. View Article : Google Scholar : PubMed/NCBI
15	LaMonte BH, Wallace KE, Holloway BA, Shelly SS, Ascaño J, Tokito M, Van Winkle T, Howland DS and Holzbaur EL: Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron. 34:715–727. 2002. View Article : Google Scholar : PubMed/NCBI
16	Hafezparast M, Klocke R, Ruhrberg C, Marquardt A, Ahmad-Annuar A, Bowen S, Lalli G, Witherden AS, Hummerich H, Nicholson S, et al: Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science. 300:808–812. 2003. View Article : Google Scholar : PubMed/NCBI
17	Paternostro-Sluga T, Grim-Stieger M, Posch M, Schuhfried O, Vacariu G, Mittermaier C, Bittner C and Fialka-Moser V: Reliability and validity of the Medical Research Council (MRC) scale and a modified scale for testing muscle strength in patients with radial palsy. J Rehabil Med. 40:665–671. 2008. View Article : Google Scholar : PubMed/NCBI
18	Birouk N, Gouider R, Le Guern E, Gugenheim M, Tardieu S, Maisonobe T, Le Forestier N, Agid Y, Brice A and Bouche P: Charcot-Marie-Tooth disease type 1A with 17p11.2 duplication. Clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases. Brain. 120:813–823. 1997. View Article : Google Scholar : PubMed/NCBI
19	Choi BO, Kim J, Lee KL, Yu JS, Hwang JH and Chung KW: Rapid diagnosis of CMT1A duplications and HNPP deletions by multiplex microsatellite PCR. Mol Cells. 23:39–48. 2007.PubMed/NCBI
20	Sanger F, Nicklen S and Coulson AR: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA. 74:5463–5467. 1977. View Article : Google Scholar : PubMed/NCBI
21	Tamura K, Peterson D, Peterson N, Stecher G, Nei M and Kumar S: MEGA5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol. 28:2731–2739. 2011. View Article : Google Scholar : PubMed/NCBI