{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:53:54Z","timestamp":1772931234304,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["Ga354\/14-1"],"award-info":[{"award-number":["Ga354\/14-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["941\/2-5"],"award-info":[{"award-number":["941\/2-5"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010570","name":"Nieders\u00e4chsisches Ministerium f\u00fcr Wissenschaft und Kultur","doi-asserted-by":"publisher","award":["11-76251-12-4\/12 (ZN2938)"],"award-info":[{"award-number":["11-76251-12-4\/12 (ZN2938)"]}],"id":[{"id":"10.13039\/501100010570","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>TAF8 is part of the transcription factor II D complex, composed of the TATA-binding protein and 13 TATA-binding protein\u2013associated factors (TAFs). Transcription factor II D is the first general transcription factor recruited at promoters to assemble the RNA polymerase II preinitiation complex. So far disorders related to variants in 5 of the 13 subunits of human transcription factor II D have been described. Recently, a child with a homozygous c.781-1G&amp;gt;A mutation in TAF8 has been reported. Here we describe seven further patients with mutations in TAF8 and thereby confirm the TAF8 related disorder.<\/jats:p><jats:p>In two sibling patients, we identified two novel compound heterozygous TAF8 splice site mutations, c.45+4A\u2009&amp;gt;\u2009G and c.489G&amp;gt;A, which cause aberrant splicing as well as reduced expression and mislocalization of TAF8. In five further patients, the previously described c.781-1G\u2009&amp;gt;\u2009A mutation was present on both alleles. The clinical phenotype associated with the different TAF8 mutations is characterized by severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Cerebral imaging showed hypomyelination, a thin corpus callosum and brain atrophy. Moreover, repeated imaging in the sibling pair demonstrated progressive cerebral and cerebellar atrophy. Consistently, reduced N-acetylaspartate, a marker of neuronal viability, was observed on magnetic resonance spectroscopy.<\/jats:p><jats:p>Further review of the literature shows that mutations causing a reduced expression of transcription factor II D subunits have an overlapping phenotype of microcephaly, developmental delay and intellectual disability. Although transcription factor II D plays an important role in RNA polymerase II transcription in all cells and tissues, the symptoms associated with such defects are almost exclusively neurological. This might indicate a specific vulnerability of neuronal tissue to widespread deregulation of gene expression as also seen in Rett syndrome or Cornelia de Lange syndrome.<\/jats:p>","DOI":"10.1093\/brain\/awac154","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T12:45:55Z","timestamp":1650977155000},"page":"3022-3034","source":"Crossref","is-referenced-by-count":9,"title":["Mutations in<i>TAF8<\/i>cause a neurodegenerative disorder"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5449-6318","authenticated-orcid":false,"given":"Keit Men","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Neuropediatrics, Jena University Hospital , 07747 Jena , Germany"},{"name":"Center for Rare Diseases, Jena University Hospital , 07747 Jena , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne M","family":"Jepsen","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute, Neurogenomics Division\u2014Huentelman Lab , Phoenix, AZ 85004 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Efthymiou","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders, UCL Institute of Neurology , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Salpietro","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders, UCL Institute of Neurology , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith","family":"Sanchez-Castillo","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute, Neurogenomics Division\u2014Huentelman Lab , Phoenix, AZ 85004 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janice","family":"Yip","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders, UCL Institute of Neurology , London WC1N 3BG , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamna","family":"Kriouile","sequence":"additional","affiliation":[{"name":"Unit of Neuropediatrics and Neurometabolism, Pediatric Department 2, Rabat Children\u2019s Hospital , BP 6527 Rabat , Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9134-6303","authenticated-orcid":false,"given":"Susann","family":"Diegmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Neurology, University Medical Center G\u00f6ttingen , 37075 Goettingen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffi","family":"Dreha-Kulaczewski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Neurology, University Medical Center G\u00f6ttingen , 37075 Goettingen , 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(CCG) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne , 50931 Cologne , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehran Beiraghi","family":"Toosi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Ghaem Hospital, Mashhad University of Medical Sciences , Mashhad 45785 , Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javad","family":"Akhondian","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Ghaem Hospital, Mashhad University of Medical Sciences , Mashhad 45785 , Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehsan","family":"Ghayoor Karimiani","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Institute, St. George\u2019s, University of London , Cranmer Terrace, London SW17 0RE , UK"},{"name":"Innovative Medical Research Center, Mashhad Branch, Islamic Azad University , Mashhad 45785 , Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Hummel-Abmeier","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Neurology, University Medical Center G\u00f6ttingen , 37075 Goettingen , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda","family":"Huppke","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Jena University Hospital , 07747 Jena , Germany"},{"name":"Center for Rare Diseases, Jena University Hospital , 07747 Jena , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-7777","authenticated-orcid":false,"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders, UCL Institute of Neurology , London WC1N 3BG , 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