Clinical and genetic analysis of ATP13A2 in hereditary spastic paraplegia expands the phenotype.
Mol Genet Genomic Med
; 8(3): e1052, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31944623
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paraplegia
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Fenótipo
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ATPases Translocadoras de Prótons
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Mol Genet Genomic Med
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá