Parkinson Disease and Complex Parkinsonism
Gene: TAF1
Hemizygous mutations cause severe progressive torsion dystonia and parkinsonism, affecting primarily males from the Panay Island, Philippines. All known cases to date are in individuals of Filipino descent (PMID: 20301662). The progressive torsion dystonia-parkinsonism is associated to an haplotype containing 5 disease-specific single-nucleotide changes (DSC1, 2, 3, 10, and 12) (PMID: 12928496). Deep sequencing of the disease-associated haplotype identified disease-specific SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) in intron 32 of the TAF1 gene. The insertion is 2,627 bp in length. Hemizygous mutations also cause X-linked ID (26637982). Keep this gene in both this gene to both the dystonia panel and pdCreated: 14 Dec 2016, 5:27 p.m.
Comment on list classification: Is on the Complex Parkinson's Disease/Dystonia NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual. Feedback from Huw Morris (UCL): has only been reported in a population in the Philippines. PMID: 17273961 - Study of 67 Filipino individuals (affected males) from 16 families in Panay. All patients had the disease-specific haplotype between DXS10017 and DXS10018 in the DYT3 region. They report finding a short interspersed nuclear element, variable number of tandem repeats and Alu composite retrotransposon insertion in an intron of TAF1, as well as an abnormal pattern of DNA methylation. A comment on this paper is found here: PMID: 17668393. Expression of this gene seems to be involved in the disorder, however whether loss of function variants within this gene would be causative is not clear. TAF1 variants have been reported to be associated with global developmental delay, intellectual disability (ID), characteristic facial dysmorphology, generalized hypotonia, and variable neurologic features, in male individuals PMID: 26637982.Created: 10 Jun 2016, 11:36 a.m.
19th Dec 2016: panel revised according to expert review and further curation.
Mode of pathogenicity for TAF1 was changed to Other - please provide details in the comments
Publications for TAF1 were set to 17273961; 17668393; 26637982; 20301662;12928496
Publications for TAF1 were set to 17273961; 17668393; 26637982;20301662
Publications for TAF1 were set to 17273961;17668393;26637982
Publications for TAF1 were set to 17273961
This gene has been classified as Amber List (Moderate Evidence).
TAF1 was added to Parkinson Disease and Complex Parkinsonismpanel. Sources: Radboud University Medical Center, Nijmegen
TAF1 was created by ellenmcdonagh