Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7

Giulia Coarelli, Rebecca Schule, Bart P.C. van de Warrenburg, Peter De Jonghe, Claire Ewenczyk, Andrea Martinuzzi, Matthis Synofzik, Elisa G. Hamer, Jonathan Baets, Mathieu Anheim, Ludger Schöls, Tine Deconinck, Pegah Masrori, Bertrand Fontaine, Thomas Klockgether, Maria Grazia D'Angelo, Marie Lorraine Monin, Jan De Bleecker, Isabelle Migeotte, Perrine CharlesMaria Teresa Bassi, Thomas Klopstock, Fanny Mochel, Elisabeth Ollagnon-Roman, Marc D'Hooghe, Christoph Kamm, Delia Kurzwelly, Melanie Papin, Claire Sophie Davoine, Guillaume Banneau, Sophie Tezenas du Montcel, Danielle Seilhean, Alexis Brice, Charles Duyckaerts, Giovanni Stevanin, Alexandra Durr

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)e2679-e2690
Number of pages12
Issue number23
Publication statusPublished - Jun 4 2019

ASJC Scopus subject areas

  • Clinical Neurology

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