Hehr, Ure and Bauer, Peter and Winner, Beate and Schule, Rebecca and Olmez, Akguen and Koehler, Wolfgang and Uyanik, Goelchan and Engel, Anna and Lenz, Damela and Seibel, Andrea and Hehr, Andreas and Ploetz, Sonja and Gamez, Josep and Rolfs, Arndt and Weis, Joachim and Ringer, Thomas M. and Bonin, Michael and Schuierer, Gerhard and Marienhagen, Joerg and Bogdahn, Ulrich and Weber, Bernhard H. F. and Topaloglu, Haluk and Schols, Ludger and Riess, Olaf and Winkler, Juergen (2007) Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia. ANNALS OF NEUROLOGY, 62 (6). pp. 656-665. ISSN 0364-5134,
Full text not available from this repository. (Request a copy)Abstract
Objective: Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of neurodegenerative disorders resulting in progressive spasticity of the lower limbs. One form of autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) was linked to chromosomal region 15q13-21 (SPG11) and associated with mutations in the spatacsin gene. We assessed the long-term course and the mutational spectrum of spatacsin-associated ARHSP with TCC. Methods: Neurological examination, cerebral magnetic resonance imaging (MRI), (18)fluorodeoxyglucose positron emission tomography (PET), nerve biopsy, linkage and mutation analysis are presented. Results: Spastic paraplegia in patients with spatacsin mutations (n=20) developed during the second decade of life. The Spastic Paraplegia Rating Scale (SPRS) showed severely compromised walking between the second and third decades of life (mean SPRS score, > 30). Impaired cognitive function was associated with severe atrophy of the frontoparietal cortex, TCC, and bilateral periventricular white matter lesions. Progressive cortical and thalamic hypometabolism in the (18)fluorodeoxyglucose PET was observed. Sural nerve biopsy showed a loss of unmyelinated nerve fibers and accumulation of intraaxonal pleomorphic membranous material. Mutational analysis of spatacsin demonstrated six novel and one previously reported frameshift mutation and two novel nonsense mutations. Furthermore, we report the first two splice mutations to be associated with SPG 11. Interpretation: We demonstrate that not only frameshift and nonsense mutations but also splice mutations result in SPG 11. Mutations are distributed throughout the spatacsin gene and emerge as major cause for ARHSP with TCC associated with severe motor and cognitive impairment. The clinical phenotype and the ultrastructural analysis suggest a disturbed axonal transport of long projecting neurons.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THIN CORPUS-CALLOSUM; SPG11; PROGRESSION; DEFICIENCY; ADULTHOOD; 15Q13-15; DATABASE; DISEASE; LINKAGE; LOCUS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik Medicine > Lehrstuhl für Neurologie Medicine > Abteilung für Nuklearmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Nov 2020 08:10 |
| Last Modified: | 25 Nov 2020 08:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31819 |
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