dc.contributor.author | Hewamadduma, Channa A. | en |
dc.contributor.author | Hoggard, Nigel | en |
dc.contributor.author | O'Malley, Ronan | en |
dc.contributor.author | Robinson, Megan K. | en |
dc.contributor.author | Beauchamp, Nick J. | en |
dc.contributor.author | Segamogaite, Ruta | en |
dc.contributor.author | Martindale, Jo | en |
dc.contributor.author | Rodgers, Tobias | en |
dc.contributor.author | Rao, Ganesh | en |
dc.contributor.author | Sarrigiannis, Ptolemaios | en |
dc.contributor.author | Shanmugarajah, Priya | en |
dc.contributor.author | Zis, Panagiotis | en |
dc.contributor.author | Sharrack, Basil | en |
dc.contributor.author | McDermott, Christopher J. | en |
dc.contributor.author | Shaw, Pamela J. | en |
dc.contributor.author | Hadjivassiliou, Marios | en |
dc.creator | Hewamadduma, Channa A. | en |
dc.creator | Hoggard, Nigel | en |
dc.creator | O'Malley, Ronan | en |
dc.creator | Robinson, Megan K. | en |
dc.creator | Beauchamp, Nick J. | en |
dc.creator | Segamogaite, Ruta | en |
dc.creator | Martindale, Jo | en |
dc.creator | Rodgers, Tobias | en |
dc.creator | Rao, Ganesh | en |
dc.creator | Sarrigiannis, Ptolemaios | en |
dc.creator | Shanmugarajah, Priya | en |
dc.creator | Zis, Panagiotis | en |
dc.creator | Sharrack, Basil | en |
dc.creator | McDermott, Christopher J. | en |
dc.creator | Shaw, Pamela J. | en |
dc.creator | Hadjivassiliou, Marios | en |
dc.date.accessioned | 2021-02-23T14:38:37Z | |
dc.date.available | 2021-02-23T14:38:37Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 2376-7839 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/64190 | |
dc.description.abstract | Objective To clinically, genetically, and radiologically characterize a large cohort of SPG7 patients. Methods We used data from next-generation sequencing panels for ataxias and hereditary spastic paraplegia to identify a characteristic phenotype that helped direct genetic testing for variations in SPG7 . We analyzed MRI. We reviewed all published SPG7 mutations for correlations. Results We identified 42 cases with biallelic SPG7 mutations, including 7 novel mutations, including a large multi-exon deletion, representing one of the largest cohorts so far described. We identified a characteristic phenotype comprising cerebellar ataxia with prominent cerebellar dysarthria, mild lower limb spasticity, and a waddling gait, predominantly from a cohort of idiopathic ataxia. We report a rare brain MRI finding of dentate nucleus hyperintensity on T2 sequences with SPG7 mutations. We confirm that the c.1529C>T allele is frequently present in patients with long-standing British ancestry. Based on the findings of the present study and existing literature, we confirm that patients with homozygous mutations involving the M41 peptidase domain of SPG7 have a younger age at onset compared to individuals with mutations elsewhere in the gene (14 years difference, p < 0.034), whereas c.1529C>T compound heterozygous mutations are associated with a younger age at onset compared to homozygous cases (5.4 years difference, p < 0.022). Conclusions Mutant SPG7 is common in sporadic ataxia. In patients with British ancestry, c.1529C>T allele represents the most frequent mutation. SPG7 mutations can be clinically predicted by the characteristic hybrid spastic-ataxic phenotype described above, along with T2 hyperintensity of the dentate nucleus on MRI. | en |
dc.language.iso | en | en |
dc.source | Neurology Genetics | en |
dc.source.uri | http://ng.neurology.org/lookup/doi/10.1212/NXG.0000000000000279 | |
dc.title | Novel genotype-phenotype and MRI correlations in a large cohort of patients with <i>SPG7</i> mutations | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1212/NXG.0000000000000279 | |
dc.description.volume | 4 | |
dc.description.issue | 6 | |
dc.author.faculty | Ιατρική Σχολή / Medical School | |
dc.author.department | Ιατρική Σχολή / Medical School | |
dc.type.uhtype | Article | en |
dc.source.abbreviation | Neurol Genet | en |
dc.contributor.orcid | Zis, Panagiotis [0000-0001-8567-3092] | |
dc.contributor.orcid | Hadjivassiliou, Marios [0000-0003-2542-8954] | |
dc.contributor.orcid | Sarrigiannis, Ptolemaios [0000-0002-8380-8755] | |
dc.gnosis.orcid | 0000-0001-8567-3092 | |
dc.gnosis.orcid | 0000-0003-2542-8954 | |
dc.gnosis.orcid | 0000-0002-8380-8755 | |