Two novel mutations in the Spastin gene of Chinese patients with hereditary spastic paraplegia

Authors

  • Q.-Z. Fei,

    1.  Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
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    • These authors contributed equally to this work.

  • W.-G. Tang,

    1.  Department of Neurology, Zhoushan Hospital, Zhejiang, China
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    • These authors contributed equally to this work.

  • T.-Y. Rong,

    1.  Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
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    • These authors contributed equally to this work.

  • H.-D. Tang,

    1.  Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
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  • J.-R. Liu,

    1.  Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
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  • Z.-L. Guo,

    1.  Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
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  • Y. Fu,

    1.  Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
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  • Q. Xiao,

    1.  Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
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  • X.-J. Wang,

    1.  Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
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  • S.-B. He,

    1.  Department of Neurology, Zhoushan Hospital, Zhejiang, China
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  • L. Cao,

    1.  Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
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  • S.-D. Chen

    1.  Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai
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Sheng-Di Chen, Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China (tel/fax: +86 21 64457249; e-mail: chen_sd@medmail.com.cn); Li Cao, Department of Neurology and Institute of Neurology, Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China (tel/fax: +86 21 64457249; e-mail: caoli_csu@yahoo.com.cn); Song-Bin He, Department of Neurology, Zhoushan Hospital, Zhejiang 316004, China (tel/fax: +86 580 2558005; e-mail: 1998hsb@163.com).

Abstract

Background and purpose:  Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative diseases. Mutations in the spastin (SPG4) gene are responsible for approximately 40% of autosomal dominant HSP (AD-HSP) and 6.5–18% of sporadic cases.

Methods:  Spastin mutations were screened in 11 AD-HSP families and 11 sporadic cases by direct sequencing and MLPA assay. Novel mutations were detected in 100 healthy controls by PCR-RFLP.

Results:  We identified seven different spastin mutations in five probands and one sporadic patient. Two of seven mutations were novel. The c.458delT was a pathogenic mutation, but the effect of c.1724 G>T remained unknown.

Conclusions:  This study allowed us to estimate the frequency of the SPG4 mutations in Chinese at 45% (5/11) in families with AD-HSP and 9% (1/11) in sporadic cases. In addition, our data showed p.T614I was not associated with congenital arachnoid cysts.

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