biostudies-literatureHayer SNNINDS NIH HHS31https://www.ebi.ac.uk/biostudies/studies/S-EPMC5307643biostudies-literatureUnknown12(1)<h4>Background</h4>CHIP, the protein encoded by STUB1, is a central component of cellular protein homeostasis and interacts with several key proteins involved in the pathogenesis of manifold neurodegenerative diseases. This gives rise to the hypothesis that mutations in STUB1 might cause a far more multisystemic neurodegenerative phenotype than the previously reported cerebellar ataxia syndrome.<h4>Methods</h4>Whole exome sequencing data-sets from n = 87 index subjects of two ataxia cohorts were screened for individuals with STUB1 mutations. In-depth phenotyping by clinical evaluation and neuroimaging was performed in mutation carriers.<h4>Results</h4>We identified four novel STUB1 mutations in three affected subjects from two index families (frequency 2/87 = 2.3%). All three subjects presOrphanet journal of rare diseasesSTUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations.PMC5307643R01 NS072248R01 NS054132U54 NS065712R01 NS075764Bender BReich SHayer SNDe Jonghe PBaets JZuchner SSynofzik MDeconinck TSchols LSchule RSmets KfalseSTUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations.<h4>Background</h4>CHIP, the protein encoded by STUB1, is a central component of cellular protein homeostasis and interacts with several key proteins involved in the pathogenesis of manifold neurodegenerative diseases. This gives rise to the hypothesis that mutations in STUB1 might cause a far more multisystemic neurodegenerative phenotype than the previously reported cerebellar ataxia syndrome.<h4>Methods</h4>Whole exome sequencing data-sets from n = 87 index subjects of two ataxia cohorts were screened for individuals with STUB1 mutations. In-depth phenotyping by clinical evaluation and neuroimaging was performed in mutation carriers.<h4>Results</h4>We identified four novel STUB1 mutations in three affected subjects from two index families (frequency 2/87 = 2.3%). All three subjects pres2017-01-01T00:00:00Z2017 Feb2026-07-16T00:09:11.147Z2026-07-09T10:26:11.163ZS-EPMC53076432819327310.1186/s13023-017-0580-x