| Title: |
Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7 |
| Authors: |
Coarelli, G; Schule, R; van de Warrenburg, BPC; De Jonghe, P; Ewenczyk, C; Martinuzzi, A; Synofzik, M; Hamer, EG; Baets, J; Anheim, M; Schöls, L; Deconinck, T; Masrori, P; Fontaine, B; Klockgether, T; D'Angelo, MG; Monin, ML; De Bleecker, Jan; Migeotte, I; Charles, P; Bassi, MT; Klopstock, T; Mochel, F; Ollagnon-Roman, E; D'Hooghe, M; Kamm, C; Kurzwelly, D; Papin, M; Davoine, CS; Banneau, G; Tezenas du Montcel, S; Seilhean, D; Brice, A; Duyckaerts, C; Stevanin, G; Durr, A |
| Source: |
NEUROLOGY ; ISSN: 0028-3878 ; ISSN: 1526-632X |
| Publication Year: |
2019 |
| Collection: |
Ghent University Academic Bibliography |
| Subject Terms: |
Medicine and Health Sciences; M-AAA PROTEASE; MUTATIONS; GENE; DISEASE; SCALE |
| Description: |
Objective : We took advantage of a large multinational recruitment to delineate genotype-phenotype correlations in a large, trans-European multicenter cohort of patients with spastic paraplegia gene 7 (SPG7). Methods : We analyzed clinical and genetic data from 241 patients with SPG7, integrating neurologic follow-up data. One case was examined neuropathologically. Results : Patients with SPG7 had a mean age of 35.5 +/- 14.3 years (n = 233) at onset and presented with spasticity (n = 89), ataxia (n = 74), or both (n = 45). At the first visit, patients with a longer disease duration (> 20 years, n = 62) showed more cerebellar dysarthria (p < 0.05), deep sensory loss (p < 0.01), muscle wasting (p < 0.01), ophthalmoplegia (p < 0.05), and sphincter dysfunction (p < 0.05) than those with a shorter duration (< 10 years, n = 93). Progression, measured by Scale for the Assessment and Rating of Ataxia evaluations, showed a mean annual increase of 1.0 +/- 1.4 points in a subgroup of 30 patients. Patients homozygous for loss of function (LOF) variants (n = 65) presented significantly more often with pyramidal signs (p < 0.05), diminished visual acuity due to optic atrophy (p < 0.0001), and deep sensory loss (p < 0.0001) than those with at least 1 missense variant (n = 176). Patients with at least 1 Ala510Val variant (58%) were older (age 37.6 +/- 13.7 vs 32.8 +/- 14.6 years, p < 0.05) and showed ataxia at onset (p < 0.05). Neuropathologic examination revealed reduction of the pyramidal tract in the medulla oblongata and moderate loss of Purkinje cells and substantia nigra neurons. Conclusions : This is the largest SPG7 cohort study to date and shows a spasticity-predominant phenotype of LOF variants and more frequent cerebellar ataxia and later onset in patients carrying at least 1 Ala510Val variant. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://biblio.ugent.be/publication/8618345; https://doi.org/10.1212/wnl.0000000000007606; https://biblio.ugent.be/publication/8618345/file/8618347 |
| DOI: |
10.1212/wnl.0000000000007606 |
| Availability: |
https://biblio.ugent.be/publication/8618345; https://hdl.handle.net/1854/LU-8618345; https://doi.org/10.1212/wnl.0000000000007606; https://biblio.ugent.be/publication/8618345/file/8618347 |
| Rights: |
info:eu-repo/semantics/restrictedAccess |
| Accession Number: |
edsbas.5B4473D7 |
| Database: |
BASE |