Title | Clinical and genetic analysis of ATP13A2 in hereditary spastic paraplegia expands the phenotype. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Auteurs | Estiar, MA, Leveille, E, Spiegelman, D, Dupré, N, Trempe, J-F, Rouleau, GA, Gan-Or, iv, Z |
Journal | Mol Genet Genomic Med |
Pagination | e1052 |
Date Published | 2020 Jan 15 |
ISSN | 2324-9269 |
Abstract | BACKGROUND: Hereditary spastic paraplegias (HSP) are neurodegenerative disorders characterized by lower limb spasticity and weakness, with or without additional symptoms. Mutations in ATP13A2, known to cause Kufor-Rakeb syndrome (KRS), have been recently implicated in HSP.METHODS: Whole-exome sequencing was done in a Canada-wide HSP cohort.RESULTS: Three additional patients with homozygous ATP13A2 mutations were identified, representing 0.7% of all HSP families. Spastic paraplegia was the predominant feature, all patients suffered from psychiatric symptoms, and one patient had developed seizures. Of the identified mutations, c.2126G>C;(p.[Arg709Thr]) is novel, c.2158G>T;(p.[Gly720Trp]) has not been reported in ATP13A2-related diseases, and c.2473_2474insAAdelC;p.[Leu825Asnfs*32]) has been previously reported in KRS but not in HSP. Structural analysis of the mutations suggested a disruptive effect, and enrichment analysis suggested the potential involvement of specific pathways.CONCLUSION: Our study suggests that in HSP patients with psychiatric symptoms, ATP13A2 mutations should be suspected, especially if they also have extrapyramidal symptoms. |
DOI | 10.1002/mgg3.1052 |
Alternate Journal | Mol Genet Genomic Med |
PubMed ID | 31944623 |
Grant List | RN127580 - 260005 / / CIHR Emerging Team Grant / / / CIHR Foundation / |