Early onset dystonia
Gene: TAF1
Comment from the Parkinson panel: 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: 15 Dec 2016, 11:10 a.m.
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.Created: 10 Jun 2016, 8:58 a.m.
Comment on list classification: This gene is on the 19 gene NGS panel in development on the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual for dystonia.Created: 10 Jun 2016, 7:34 a.m.
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: 9 Jun 2016, 11:19 a.m.
Comment on list classification: Feedback from Huw Morris (UCL): has only been reported in a population in the Philippines.Created: 9 Jun 2016, 11:13 a.m.
Comment on list classification: On GeneReviews confirmed list.Created: 27 May 2016, 8:58 a.m.
17th Oct 2016: Promoted to version 1. The panel was revised after expert input and internal discussion with the clinical team. Other panels such as hereditary ataxia or dementia may be applied in conjunction with this panel where appropriate for genome analysis.
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Red List (Low Evidence).
Publications for TAF1 were set to http://www.ncbi.nlm.nih.gov/books/NBK1155/; PMID: 2368812; PMID: 12928496; PMID: 17273961; PMID: 26879577; PMID: 26769797; PMID: 26637982; PMID: 23184149
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Green List (High Evidence).
Publications for TAF1 were set to http://www.ncbi.nlm.nih.gov/books/NBK1155/
This gene has been classified as Green List (High Evidence).
Model of inheritance for gene TAF1 was changed to X-LINKED: hemizygous mutation in males, may be caused by monoallelic mutations in females
TAF1 was added to Early onset dystoniapanel. Sources: Expert
TAF1 was added to Early onset dystoniapanel. Sources: Emory Genetics Laboratory
TAF1 was added to Early onset dystoniapanel. Sources: Radboud University Medical Center, Nijmegen