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Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis

Lookup NU author(s): Dr Janet Lindsey, Dr Meryl Lusher, Dr Kathleen White, Dr Rumaisa Bashir, Professor Pamela Shaw, Emerita Professor Katherine Bushby


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Background-Hereditary spastic paraparesis is a genetically heterogeneous condition. Recently, mutations in the spastin gene were reported in families Linked to the common SPG4 locus on chromosome 2p21-22. Objectives-To study a population of patients with hereditary spastic paraparesis for mutations in the spastin gene (SPG4) on chromosome 2p21-22. Methods-DNA from 32 patients (12 from families known to be linked to SPG4) was analysed for mutations in the spastin gene by single strand conformational polymorphism analysis and sequencing. All patients were also examined clinically. Results-Thirteen SPG4 mutations were identified, 11 of which are novel. These mutations include missense, nonsense, frameshift, and splice site mutations, the majority of which affect the AAA cassette. We also describe a nucleotide substitution outside this conserved region which appears to behave as a recessive mutation. Conclusions-Recurrent mutations in the spastin gene are uncommon. This reduces the ease of mutation detection as a part of the diagnostic work up of patients with hereditary spastic paraparesis. Our findings have important implications for the presumed function of spastin and schemes for mutation detection in HSP patients.

Publication metadata

Author(s): Lindsey JC, Lusher ME, McDermott CJ, White KD, Reid E, Rubinsztein DC, Bashir R, Hazan J, Shaw PJ, Bushby KMD

Publication type: Article

Publication status: Published

Journal: Journal of Medical Genetics

Year: 2000

Volume: 37

Issue: 10

Pages: 759-765

ISSN (print): 0022-2593

ISSN (electronic): 1468-6244

Publisher: BMJ Group


DOI: 10.1136/jmg.37.10.759


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