These authors contributed equally to this work.
Large deletion mutation of SPAST in a multi-generation family from Sardinia
Article first published online: 4 NOV 2013
© 2013 The Author(s) European Journal of Neurology © 2013 EAN
European Journal of Neurology
Volume 21, Issue 6, pages 935–938, June 2014
How to Cite
Racis, L., Di Fabio, R., Tessa, A., Guillot, F., Storti, E., Piccolo, F., Nesti, C., Tedde, A., Pierelli, F., Agnetti, V., Santorelli, F. M. and Casali, C. (2014), Large deletion mutation of SPAST in a multi-generation family from Sardinia. European Journal of Neurology, 21: 935–938. doi: 10.1111/ene.12290
- Issue published online: 8 MAY 2014
- Article first published online: 4 NOV 2013
- Manuscript Accepted: 23 SEP 2013
- Manuscript Received: 7 JUN 2013
- HSP ;
Background and purpose
The hereditary spastic paraplegias (HSP) are characterized by progressive spasticity of the lower limbs, mostly inherited as an autosomal dominant trait. Analyses of large HSP pedigrees could help to better characterize the phenotype due to a single causative mutation. Patients in a seven-generation kindred carrying a large deletion in SPAST/SPG4 are described.
Individuals originating from Sardinia were clinically and genetically studied.
Sixty-seven subjects carried a heterozygous deletion encompassing exons 2–17 of SPAST. Fifty patients (53.2 ± 15.4 years) presented a pure form of spastic paraparesis characterized by mild impairment and slow progression. Most patients showed spasticity, increased tendon reflexes in the lower limbs and Babinski sign, whilst weakness was rarely detected and urinary disturbances occasionally reported. Amongst the 17 asymptomatic carriers of the mutation, minimal neurological signs were detected in 11 cases.
A focus on spasticity, increased tendon reflexes and Babinski sign, more than on weakness, could help clinicians to promote early diagnosis in asymptomatic carriers of SPAST deletions.