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Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project.

Published version
Peer-reviewed

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Authors

Bourinaris, Thomas 
Cipriani, Valentina 
Athanasiou-Fragkouli, Alkyoni 

Abstract

Hereditary spastic paraplegia (HSP) is a group of heterogeneous inherited degenerative disorders characterized by lower limb spasticity. Fifty percent of HSP patients remain yet genetically undiagnosed. The 100,000 Genomes Project (100KGP) is a large UK-wide initiative to provide genetic diagnosis to previously undiagnosed patients and families with rare conditions. Over 400 HSP families were recruited to the 100KGP. In order to obtain genetic diagnoses, gene-based burden testing was carried out for rare, predicted pathogenic variants using candidate variants from the Exomiser analysis of the genome sequencing data. A significant gene-disease association was identified for UBAP1 and HSP. Three protein truncating variants were identified in 13 patients from 7 families. All patients presented with juvenile form of pure HSP, with median age at onset 10 years, showing autosomal dominant inheritance or de novo occurrence. Additional clinical features included parkinsonism and learning difficulties, but their association with UBAP1 needs to be established.

Description

Keywords

Adolescent, Adult, Aged, Carrier Proteins, Child, Female, Humans, Male, Middle Aged, Mutation, Phenotype, Spastic Paraplegia, Hereditary

Journal Title

Eur J Hum Genet

Conference Name

Journal ISSN

1018-4813
1476-5438

Volume Title

28

Publisher

Springer Science and Business Media LLC