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


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.

SUBMITTER: Bourinaris T 

PROVIDER: S-EPMC7784862 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Bourinaris Thomas T   Smedley Damian D   Cipriani Valentina V   Sheikh Isabella I   Athanasiou-Fragkouli Alkyoni A   Chinnery Patrick P   Morris Huw H   Real Raquel R   Harrison Victoria V   Reid Evan E   Wood Nicholas N   Vandrovcova Jana J   Houlden Henry H   Tucci Arianna A  

European journal of human genetics : EJHG 20200915 12


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  ...[more]

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