Clinical features and genetic diagnosis of hereditary spinocerebellar ataxia 3

Wang,Yaoguang; Yang,Xiaokai; Ma,Weide; Li,Jinxin; Zhang,Qingyuan; Xia,Shuqi; Wang,Hai; Zhang,Chenghui; Xu,Xiaomin; Zheng,Jiayong

doi:10.3892/mmr.2016.5707

October-2016 Volume 14 Issue 4

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

October-2016 Volume 14 Issue 4

Full Size Image

Article

Clinical features and genetic diagnosis of hereditary spinocerebellar ataxia 3

Authors:
- Yaoguang Wang
- Xiaokai Yang
- Weide Ma
- Jinxin Li
- Qingyuan Zhang
- Shuqi Xia
- Hai Wang
- Chenghui Zhang
- Xiaomin Xu
- Jiayong Zheng
View Affiliations / Copyright

Affiliations: Department of Neurology, Wenzhou City Key Laboratory of Gynecology and Obstetrics, Wenzhou People's Hospital, Wenzhou Maternal and Child Health Care Hospital, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Gynecology and Obstetrics, Wenzhou City Key Laboratory of Gynecology and Obstetrics, Wenzhou People's Hospital, Wenzhou Maternal and Child Health Care Hospital, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Pages: 3731-3734
|
Published online on: September 5, 2016

https://doi.org/10.3892/mmr.2016.5707
Expand metrics +

Abstract

Spinocerebellar ataxia type 3 (SCA3) is a rare inherited autosomal dominant progressive neurological disorder, which results from a CAG‑repeat expansion in the gene encoding the deubiquitinating enzyme, ataxin‑3. At present, no effective treatment is available for this fatal disorder; however, certain studies have suggested that reducing the levels of mutant ataxin‑3 protein may reverse or halt the progression of disease in patients with SCA3. In the present study, clinical examinations were performed on a patient with SCA3 who exhibited disease features including coughing, expectoration and was bedridden with mobility limitation. CAG repetitions at SCA‑associated genes were detected in the patient's family by performing standard polymerase chain reaction (PCR) and triple‑repeat primed PCR. The numbers of CAG‑repeats within the two alleles of the gene of interest in the patient were 15 and 78. Notably, the patient's brother, who harbored 76 CAG‑repeats in one allele of the gene of interest, did not exhibit severe disease symptoms. These results suggest that the number of CAG‑repeats is a critical for determination of SCA3 disease severity and time of onset. In addition, the deﬁned phenotypic characteristics of the patient in the present study provide useful insight for more accurate clinical diagnosis and genotyping of future patients.

View Figures

View References

1	Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I, et al: CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet. 8:221–228. 1994. View Article : Google Scholar : PubMed/NCBI
2	Nakano KK, Dawson DM and Spence A: Machado disease. A hereditary ataxia in Portuguese emigrants to Massachusetts. Neurology. 22:49–55. 1972. View Article : Google Scholar : PubMed/NCBI
3	Rosenberg RN, Nyhan WL, Bay C and Shore P: Autosomal dominant striatonigral degeneration. A clinical, pathologic, and biochemical study of a new genetic disorder. Neurology. 26:703–714. 1976. View Article : Google Scholar : PubMed/NCBI
4	Zhou YX, Takiyama Y, Igarashi S, Li YF, Zhou BY, Gui DC, Endo K, Tanaka H, Chen ZH, Zhou LS, et al: Machado-Joseph disease in four Chinese pedigrees: Molecular analysis of 15 patients including two juvenile cases and clinical correlations. Neurology. 48:482–485. 1997. View Article : Google Scholar : PubMed/NCBI
5	Maciel P, Gaspar C, DeStefano AL, Silveira I, Coutinho P, Radvany J, Dawson DM, Sudarsky L, Guimarães J, Loureiro JE, et al: Correlation between CAG repeat length and clinical features in Machado-Joseph disease. Am J Hum Genet. 57:54–61. 1995.PubMed/NCBI
6	Harding AE: Clinical features and classification of inherited ataxias. Adv Neurol. 61:1–14. 1993.PubMed/NCBI
7	Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, Dobyns WB, Subramony SH, Zoghbi HY and Lee CC: Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet. 15:62–69. 1997. View Article : Google Scholar : PubMed/NCBI
8	Stevanin G, Giunti P, Belal GD, Dürr A, Ruberg M, Wood N and Brice A: De novo expansion of intermediate alleles in spinocerebellar ataxia 7. Hum Mol Genet. 7:1809–1813. 1998. View Article : Google Scholar : PubMed/NCBI
9	Sanpei K, Takano H, Igarashi S, Sato T, Oyake M, Sasaki H, Wakisaka A, Tashiro K, Ishida Y, Ikeuchi T, et al: Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nat Genet. 14:277–284. 1996. View Article : Google Scholar : PubMed/NCBI
10	Koide R, Ikeuchi T, Onodera O, Tanaka H, Igarashi S, Endo K, Takahashi H, Kondo R, Ishikawa A, Hayashi T, et al: Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat Genet. 6:9–13. 1994. View Article : Google Scholar : PubMed/NCBI
11	Lin Y, Zheng JY, Jin YH, Xie YC and Jin ZB: Trinucleotide expansions in the SCA7 gene in a large family with spinocerebellar ataxia and craniocervical dystonia. Neurosci Lett. 434:230–233. 2008. View Article : Google Scholar : PubMed/NCBI
12	Todi SV, Scaglione KM, Blount JR, Basrur V, Conlon KP, Pastore A, Elenitoba-Johnson K and Paulson HL: Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117. J Biol Chem. 285:39303–39313. 2010. View Article : Google Scholar : PubMed/NCBI
13	Reina CP, Zhong X and Pittman RN: Proteotoxic stress increases nuclear localization of ataxin-3. Hum Mol Genet. 19:235–249. 2010. View Article : Google Scholar
14	Warner JP, Barron LH, Goudie D, Kelly K, Dow D, Fitzpatrick DR and Brock DJ: A general method for the detection of large CAG repeat expansions by fluorescent PCR. J Med Genet. 33:1022–1026. 1996. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Clinical features and genetic diagnosis of hereditary spinocerebellar ataxia 3

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Related Articles