Keywords
MRXS33
SVA
TAF1
Phenotypes
Submitted : 2024-09-02
Accepted : 2024-09-17
Published : 2024-10-02
Abstract
Purpose of review: TATA-binding protein (TBP)-associated factor 1 (TAF1) encodes the largest component of the transcription factor IID (TFIID) complex, which binds to core promoters and serves as a scaffold for assembly of the RNA polymerase II transcription complex. Variants in TAF1 are associated with X-linked dystonia-parkinsonism (XDP) and X-linked syndromic mental retardation-33 (MRXS33). This review provides a concise summary of the genetic and clinicopathological features of TAF1 variants related to phenotype. Recent findings: XDP is an adult-onset X-linked progressive neurodegenerative disorder presenting dystonia and parkinsonism and caused by a SINE-VNTR-Alu (SVA)-type retrotransposon within TAF1. TAF1/MRXS33 intellectual disability syndrome is characterized by global developmental delay, intellectual disability, facial dysmorphia, generalized hypotonia, and neurological abnormalities due to the missense variants in TAF1. Various symptoms of TAF1 missense mutations may be related to mutations in different functional regions of the protein. The clinical manifestations of XDP and MRXS33, both caused by variants of TAF1, present prominent heterogeneity, which could be influenced by whether the TAF1 mutation is located in the coding region, the time when TAF1 expression decreases, and the effect on downstream gene expression. Summary: TAF1 is linked to many different phenotypes because of its variable regulation of coding and noncoding elements, which makes its mechanistic roles in disease challenging to interpret. However, it is important to note that strategies to correct TAF1 splicing could provide therapeutic benefits in different diseases.
References
Gudmundsson S, Wilbe M, Filipek-Gorniok B, et al., 2019, TAF1, Associated with Intellectual Disability in Humans, is Essential for Embryogenesis and Regulates Neurodevelopmental Processes in Zebrafish. Scientific Reports, 9(1): 10730.
Aneichyk T, Hendriks WT, Yadav R, et al., 2018, Dissecting the Causal Mechanism of X-linked Dystonia-parkinsonism by Integrating Genome and Transcriptome Assembly. Cell, 172(5): 897–909.
Lee LV, Rivera C, Teleg RA, et al., 2011, The Unique Phenomenology of Sex-linked Dystonia Parkinsonism (XDP, DYT3, “Lubag”). International Journal of Neuroscience, 121(1): 3–11.
Esmaili DD, Shubin RA, Waters CH, et al., 2004, Eye Movement Abnormalities in a Case of X-linked Dystonia-Parkinsonism (Lubag). Journal of Neuro-ophthalmology, 24(2): 188–189.
Lee LV, Maranon E, Demaisip C, et al., 2002, The Natural History of Sex-linked Recessive Dystonia Parkinsonism of Panay, Philippines (XDP). Parkinsonism & Related Disorders, 9(1): 29–38.
Lee LV, Munoz E, Tan KT, et al., 2001, Sex-linked Recessive Dystonia Parkinsonism of Panay, Philippines (XDP). Molecular Pathology, 54(6): 362–368.
Jamora RDG, Ledesma LK, Domingo A, et al., 2014, Nonmotor Features in Sex-linked Dystonia Parkinsonism. Neurodegenerative Disease Management, 4(3): 283–289.
Kemmotsu N, Price CC, Oyama G, et al., 2011, Pre-and Post-GPi DBS Neuropsychological Profiles in a Case of X-linked Dystonia-parkinsonism. The Clinical Neuropsychologist, 25(1): 141–159.
Jamora RDG, Suratos CTR, Bautista JEC, et al., 2021, Neurocognitive Profile of Patients with X-linked Dystonia-parkinsonism. Journal of Neural Transmission, 128(5): 671–678.
Goto S, Lee LV, Munoz EL, et al., 2005, Functional Anatomy of the Basal Ganglia in X-linked Recessive Dystonia-parkinsonism. Annals of Neurology, 58(1): 7–17.
Pasco PM, Ison CV, Munoz EL, et al., 2010, Understanding XDP through Imaging, Pathology, and Genetics. International Journal of Neuroscience, 121(1): 12–17.
Hanssen H, Heldmann M, Prasuhn J, et al., 2018, Basal Ganglia and Cerebellar Pathology in X-linked Dystonia-parkinsonism. Brain: A Journal of Neurology, 141(10): 2995–3008.
Bragg DC, Mangkalaphiban K, Vaine CA, et al., 2017, Disease Onset in X-linked Dystonia-parkinsonism Correlates with Expansion of a Hexameric Repeat Within an SVA Retrotransposon in TAF1. Proceedings of the National Academy of Sciences of the United States of America, 114(51): E11020–E11028.
Westernberger A, Reyes CJ, Saranza G, et al., 2019, A Hexanucleotide Repeat Modified Expressivity of X-linked Dystonia Parkinsonism. Annals of Neurology, 85(6): 812–822.
Reyes CJ, Laabs BH, Schaake S, et al., 2021, Brain Regional Differences in Hexanucleotide Repeat Length in X-linked Dystonia-parkinsonism using Nanopore Sequencing. Neurology. Genetics, 7(4): e608.
O'Rawe JA, Wu Y, Dorfel MJ, et al., TAF1 Variants are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations. American Journal of Human Genetics, 97(6): 922–932.
Peng J, Wang Y, He F, et al., 2018, Novel West Syndrome Candidate Genes in a Chinese Cohort. NS Neuroscience & Therapeutics, 24(12): 1196–1206.
Cheng H, Capponi S, Wakeling E, et al., 2020, Missense Variants in TAF1 and Developmental Phenotypes: Challenges of Determining Pathogenicity. Human Mutation, 41(2): 449–464.
Hu H, Haas SA, Chelly J, et al., 2016, X-exome Sequencing of 405 Unresolved Families Identifies Seven Novel Intellectual Disability Genes. Molecular Psychiatry, 21(1): 133–148.
He M, Person TN, Hebbring SJ, et al., 2015, SeqHBase: A Big Data Toolset for Family-based Sequencing Data Analysis. Journal of Medical Genetics, 52(4): 282–288.
Morton SU, Agarwal R, Madden JA, et al., 2020, Congenital Heart Defects due to TAF1 Missense Variants. Genomic and Precision Medicine, 13(3): e002843.
Niranjan TS, Skinner C, May M, et al., 2015, Affected Kindred Analysis of Human X Chromosome Exomes to Identify Novel X-linked Intellectual Disability Genes. PloS One, 10(2): e0116454.
Taskiran EZ, Karaosmanoglu B, Kosukcu C, et al., 2021, Diagnostic Yield of Whole-Exome Sequencing in Non-syndromic Intellectual Disability. Journal of Intellectual Disability Research, 65(6): 577–588.
Hurst SE, Liktor-Busa E, Moutal A, et al., 2018, A Novel Variant in TAF1 Affects Gene Expression and is Associated with X-linked TAF1 Intellectual Disability Syndrome. Neuronal Signaling, 2(3): NS20180141.
Wang H, Curran EC, Hinds TR, et al., 2014, Crystal Structure of a TAF1-TAF7 Complex in Human Transcription Factor IID Reveals a Promoter Binding Module. Cell Research, 24(12): 1433–1444.
Peng H, Zhang S, Peng Y, et al., 2021, Yeast Bromodomain Factor 1 and its Human Homolog TAF1 Play Conserved Roles in Promoting Homologous Recombination. Advanced Science, 8(15): e2100753.
Herzfeld T, Nolte D, Muller U, 2007, Structural and Functional Analysis of the Human TAF1/DYT3 Multiple Transcript System. Mammalian Genome, 18(11): 787–795.
Domingo A, Amar D, Grutz K, et al., 2016, Evidence of TAF1 Dysfunction in Peripheral Models of X-linked Dystonia-parkinsonism. Cellular and Molecular Life Sciences, 73(16): 3205–3215.
Makino S, Kaji R, Ando S, et al., 2007, Reduced Neuron-specific expression of the TAF1 Gene is Associated with X-linked Dystonia-parkinsonism. American Journal of Human Genetics, 80(3): 393–406.
Capponi S, Stoffler N, Penney EB, et al., 2021, Dissection of TAF1 Neuronal Splicing and implications for Neurodegeneration in X-linked Dystonia-parkinsonism. Brain Communications, 3(4): fcab253.
Rakovic A, Domingo A, Grutz K, et al., 2018, Genome Editing in Induced Pluripotent Stem Cells Rescues TAF1 Levels in X-linked Dystonia-parkinsonism. Movement Disorders, 33(7): 1108–1118.
Herzfeld T, Nolte D, Grznarova M, et al., 2017, X-linked Dystonia Parkinsonism Syndrome (XDP, Lubag): Disease-specific Sequence Change DSC3 in TAF1/DYT3 Affects Genes in Vesicular Transport and Dopamine Metabolism. Human Molecular Genetics, 22(5): 941–951.
Bruggemann N, Rosales RL, Waugh JL, et al., 2017, Striatal Dysfunction in X-Linked Dystonia-parkinsonism is Associated with Disease Progression. European Journal of Neurology, 24(5): 680–686.
Walter U, Rosales R, Rocco A, et al., 2017, Sonographic Alteration of Substantia Nigra is related to Parkinsonism-predominant Course of X-linked Dystonia-parkinsonism. Parkinsonism & Related Disorders, 2017(37): 43–49.
Vaine CA, Shin D, Liu C, et al., 2017, X-linked Dystonia-parkinsonism Patient Cells Exhibit Altered Signaling via Nuclear Factor-kappa B. Neurobiology of Disease, 2017(100): 108–118.
Capetian P, Stanslowsky N, Bernhardi E, et al., 2018, Altered Glutamate Response and Calcium Dynamics in iPSC-derived Striatal Neurons from XDP Patients. Experimental Neurology, 2018(308): 47–58.
Goto S, Kawarai T, Morigaki R, et al., 2013, Defects in the Striatal Neuropeptide Y System in X-linked Dystonia-parkinsonism. Brain: A Journal of Neurology, 136(5): 1555–1567.
Cirnaru MD, Creus-Muncunill J, Nelson S, et al., 2021, Striatal Cholinergic Dysregulation after Neonatal Decrease in X-linked Dystonia Parkinsonism-related TAF1 Isoforms. Movement Disorders, 36(12): 2780–2794.
Pijnappel WWMP, Esch D, Baltissen M, et al., 2013, A Central Role for TFIID in the Pluripotent Transcription Circuitry. Nature, 2013(495): 516–519.
Walker AK, Shi Y, Blackwell TK, 2004, An Extensive Requirement for Transcription Factor IID-specific TAF-1 in Caenorhabditis elegans Embryonic Transcription. The Journal of Biological Chemistry, 279(15): 15339–15347.
Wang K, Sun F, Sheng HZ, 2006, Regulated Expression of TAF1 in 1-cell Mouse Embryos. Zygote, 14(3): 209–215.
Janakiraman U, Yu J, Moutal A, et al., 2019, TAF1-gene Editing Alters the Morphology and Function of the Cerebellum and Cerebral Cortex. Neurobiology of Disease, 2019(132): 104539
Hildebrand ME, Isope P, Miyazaki T, et al., 2009, Functional Coupling between mGluR1 and Cav3.1 T-type Calcium Channels Contributes to Parallel fiber-induced Fast Calcium Signaling Within Purkinje Cell Dendritic Spines. The Journal of Neuroscience, 29(31): 9668–9682.
Ly R, Bouvier G, Schonewille M, et al., 2013, T-type Channel Blockade Impairs Long-term Potentiation at the Parallel Fiber-Purkinje Cell Synapse and Cerebellar Learning. Proceedings of the National Academy of Sciences of the United States of America, 110(50): 20302–20307.
Janakiraman U, Dhanalakshmi C, Yu J, et al., 2020, The Investigation of the T-type Calcium Channel Enhancer SAK3 in an Animal Model of TAF1 Intellectual Disability Syndrome. Neurobiology of Disease, (143): 105006.
Dhanalakshmi C, Janakiraman U, Moutal A, et al., 2021, Evaluation of the Effects of the T-type Calcium Channel Enhancer SAK3 in a Rat Model of TAF1 Deficiency. Neurobiology of Disease, 2021(149): 105224.