A family with axonal sensorimotor polyneuropathy with TUBB3 mutation

Hong,Young   Bin; Lee,Ja   Hyun; Park,Hyung   Jun; Choi,Yu‑Ri; Hyun,Young   Se; Park,Ji   Hoon; Koo,Heasoo; Chung,Ki   Wha; Choi,Byung‑Ok

doi:10.3892/mmr.2014.3047

A family with axonal sensorimotor polyneuropathy with TUBB3 mutation

Authors:
- Young Bin Hong
- Ja Hyun Lee
- Hyung Jun Park
- Yu‑Ri Choi
- Young Se Hyun
- Ji Hoon Park
- Heasoo Koo
- Ki Wha Chung
- Byung‑Ok Choi
View Affiliations

Affiliations: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135‑710, Republic of Korea, Department of Biological Science, Kongju National University, Gongju, South Chungcheong 314‑701, Republic of Korea, Department of Pathology, Ewha Womans University School of Medicine, Seoul 120‑750, Republic of Korea
Published online on: December 4, 2014 https://doi.org/10.3892/mmr.2014.3047
Pages: 2729-2734

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Mutations in the β‑tubulin isotype III (TUBB3) gene result in TUBB3 syndrome that includes congenital fibrosis of the extraocular muscle type 3 (CFEOM3), intellectual impairments and/or an axonal sensorimotor neuropathy. In the present study, a TUBB3 D417N mutation was identified in a family with axonal sensorimotor polyneuropathy by whole exome sequencing. The proband exhibited gait disturbance at the age of 12 years and was wheelchair bound at 40 years. However, the proband's cousin exhibited gait disabilities at 45 years of age and was still able to walk when he was 60 years old. Ophthalmoplegia and intellectual impairment were not observed in either patient. A sural nerve biopsy identified an absence of large myelinated fibers without demyelinating degeneration. Based on these clinical features, the two patients exhibited an axonal peripheral neuropathy without CFEOM3. These results therefore suggested that certain TUBB3 mutations may predominantly be associated with axonal peripheral neuropathy. Furthermore, the results also suggested that TUBB3 mutations may be implicated in modulating the inter‑ and intra‑familial heterogeneity of clinical phenotypes.

View Figures

View References

1	Katsetos CD, Legido A, Perentes E and Mörk SJ: Class III beta-tubulin isotype: a key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology. J Child Neurol. 18:851–866. 2003. View Article : Google Scholar
2	Poirier K, Saillour Y, Bahi-Buisson N, et al: Mutations in the neuronal β-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects. Hum Mol Genet. 19:4462–4473. 2010. View Article : Google Scholar : PubMed/NCBI
3	Demer JL, Clark RA, Tischfield MA and Engle EC: Evidence of an asymmetrical endophenotype in congenital fibrosis of extraocular muscles type 3 resulting from TUBB3 mutations. Invest Ophthalmol Vis Sci. 51:4600–4611. 2010. View Article : Google Scholar : PubMed/NCBI
4	Tischfield MA, Baris HN, Wu C, et al: Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell. 140:74–87. 2010. View Article : Google Scholar : PubMed/NCBI
5	Jiang YQ and Oblinger MM: Differential regulation of beta III and other tubulin genes during peripheral and central neuron development. J Cell Sci. 103:643–651. 1992.PubMed/NCBI
6	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
7	Choi BO, Koo SK, Park MH, et al: Exome sequencing is an efficient tool for genetic screening of Charcot-Marie-Tooth Disease. Hum Mutat. 33:1610–1615. 2012. View Article : Google Scholar : PubMed/NCBI
8	Chung KW, Hyun YS, Lee HJ, et al: Two recessive intermediate Charcot-Marie-Tooth patients with GDAP1 mutations. J Peripher Nerv Syst. 16:143–146. 2011. View Article : Google Scholar : PubMed/NCBI
9	Birouk N, LeGuern E, Maisonobe T, et al: X-linked Charcot-Marie-Tooth disease with connexin 32 mutations: clinical and electrophysiologic study. Neurology. 50:1074–1082. 1998. View Article : Google Scholar : PubMed/NCBI
10	Shy ME, Blake J, Krajewski K, et al: Reliability and validity of the CMT neuropathy score as a measure of disability. Neurology. 64:1209–1214. 2005. View Article : Google Scholar : PubMed/NCBI
11	Choi M, Scholl UI, Ji W, et al: Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci USA. 106:19096–19101. 2009. View Article : Google Scholar : PubMed/NCBI
12	Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA and Shendure J: Exome sequencing as a tool for mendelian disease gene discovery. Nat Rev Genet. 12:745–755. 2011. View Article : Google Scholar : PubMed/NCBI
13	Ng SB, Buckingham KJ, Lee C, et al: Exome sequencing identifies the cause of a Mendelian disorder. Nat Genet. 42:30–35. 2010. View Article : Google Scholar :
14	Lee SS, Lee HJ, Park JM, et al: Proximal dominant hereditary motor and sensory neuropathy with proximal dominance association with mutation in the TRK-fused gene. JAMA Neurol. 70:607–615. 2013. View Article : Google Scholar : PubMed/NCBI
15	Nakhro K, Park JM, Hong YB, et al: SET binding factor 1 (SBF1) mutation causes Charcot-Marie-Tooth disease type 4B3. Neurology. 81:165–173. 2013. View Article : Google Scholar : PubMed/NCBI
16	Kim HJ, Hong YB, Park JM, et al: Mutations in the PLEKHG5 gene is relevant with autosomal recessive intermediate Charcot-Marie-Tooth disease. Orphanet J Rare Dis. 8:1042013. View Article : Google Scholar : PubMed/NCBI
17	Chung KW, Suh BC, Shy ME, et al: Different clinical and magnetic resonance imaging features between Charcot-Marie-Tooth disease type 1A and 2A. Neuromuscul Disord. 18:610–618. 2008. View Article : Google Scholar : PubMed/NCBI