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Year : 2016  |  Volume : 129  |  Issue : 20  |  Page : 2516-2517

A Novel Missense Mutation in the Spectrin Beta Nonerythrocytic 2 Gene Likely Associated with Spinocerebellar Ataxia Type 5

1 Department of Neurology, Chinese People's Liberation Army General Hospital, Beijing 100853, China
2 Department of Neurology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, China

Date of Submission06-Jun-2016
Date of Web Publication10-Oct-2016

Correspondence Address:
Prof. Xu-Sheng Huang
Department of Neurology, Chinese People's Liberation Army General Hospital, Beijing 100853
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0366-6999.191834

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How to cite this article:
Liu LZ, Ren M, Li M, Ren YT, Sun B, Sun XS, Chen SY, Li SY, Huang XS. A Novel Missense Mutation in the Spectrin Beta Nonerythrocytic 2 Gene Likely Associated with Spinocerebellar Ataxia Type 5. Chin Med J 2016;129:2516-7

How to cite this URL:
Liu LZ, Ren M, Li M, Ren YT, Sun B, Sun XS, Chen SY, Li SY, Huang XS. A Novel Missense Mutation in the Spectrin Beta Nonerythrocytic 2 Gene Likely Associated with Spinocerebellar Ataxia Type 5. Chin Med J [serial online] 2016 [cited 2018 Dec 11];129:2516-7. Available from: http://www.cmj.org/text.asp?2016/129/20/2516/191834

Li-Zhi Liu and Ming Ren contributed equally to this work.

To the Editor: Spinocerebellar ataxia type 5 (SCA5) is a rare autosomal dominant spinocerebellar ataxia. Mutations in the spectrin beta nonerythrocytic 2 gene (SPTBN2) are known to cause SCA5, six of which have been reported, including three missense mutations and three deletion mutations.[1]

The patient was a 19-year-old Chinese girl presenting with progressive unsteady gait while running from the age of 11 years. She was not concerned by the symptoms until a fever at the age of 18 years made her imbalance more evident. Downbeat nystagmus on bilateral gaze that was not suppressed by visual fixation was noted. Her gait was wide. The heel-knee-shin test was inaccurate and unsteady. Bilateral rebound tests were positive. Brain magnetic resonance imaging (MRI) showed marked atrophy of the cerebellar hemisphere and vermis with no evidence of abnormalities in supratentorial and brainstem structures [Figure 1].
Figure 1: Brain MRIs: Atrophy of the cerebellar hemispheres sparing the brainstem and supratentorial structures is evident (a and c; arrows). Atrophy of the cerebellar vermis is apparent (b and d; arrows). MRI: Magnetic resonance imaging.

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Based on gene sequencing, one likely candidate mutation was found in the SPTBN2 gene, a heterozygous A > G transition at nucleotide position 833 (c. 833A > G) altering codon 278, substituting arginine for histidine (p.H278R). The p.H278R variant was not found in any database of normal sequence variation. Sorts intolerant from tolerant predicted that this mutation was damaging with a score of 0.001 where less than 0.05 is considered harmful.[2] Polymorphism phenotyping v2 predicted that it was possibly damaging with a score of 0.85. A value close to 1 is suggestive that the mutation is damaging.[3]

We presented a case of SCA5 with a missense mutation in the SPTBN2 gene, which is a rare case reported worldwide. Her symptoms started at the age of eleven, which was earlier than the onset of symptoms in the German kindred, which ranged from 15 to 50 years (mean 32.8 ± 12.7 years, median 37.0 years).[4] The parents of our patient were normal clinically and based on genetic tests. Without further functional studies, we cannot confirm whether it is truly pathogenic. However, the patient experiences clinically supported spinocerebellar ataxia. In clinically appropriate patients lacking previously reported mutations, a novel missense mutation (p.H278R) in SPTBN2 should be considered.

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There are no conflicts of interest.

  References Top

Wang Y, Koh K, Miwa M, Yamashiro N, Shindo K, Takiyama Y. A Japanese SCA5 family with a novel three-nucleotide in-frame deletion mutation in the SPTBN2 gene: A clinical and genetic study. J Hum Genet 2014;59:569-73. doi: 10.1038/jhg.2014.74.  Back to cited text no. 1
Ng PC, Henikoff S. Predicting deleterious amino acid substitutions. Genome Res 2001;11:863-874. doi: 10.1101/gr.176601.  Back to cited text no. 2
Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet 2013;Chapter 7:Unit7.20. doi: 10.1002/0471142905.hg0720s76.  Back to cited text no. 3
Burk K, Zuhlke C, Konig IR, Ziegler A, Schwinger E, Globas C, et al. Spinocerebellar ataxia type 5: clinical and molecular genetic features of a German kindred. Neurology 2004;62:327-329. doi: 10.1212/01.WNL.0000103293.63340.C1.  Back to cited text no. 4


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