University of Oulu

Knuutinen, O, Pyle, A, Suo‐Palosaari, M, et al. Homozygous TAF1C variants are associated with a novel childhood‐onset neurological phenotype. Clin Genet. 2020; 98: 493– 498. https://doi.org/10.1111/cge.13827

Homozygous TAF1C variants are associated with a novel childhood‐onset neurological phenotype

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Author: Knuutinen, Oula1,2; Pyle, Angela3; Suo-Palosaari, Maria2,4;
Organizations: 1PEDEGO Research Unit, University of Oulu, Oulu, Finland
2Medical Research Center, University of Oulu, Oulu, Finland
3Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
4Department of Diagnostic Radiology, Research Unit of Medical Imaging, Physics and Technology, Oulu University Hospital and University of Oulu, Oulu, Finland
5Department of Biotechnology and Genetic Engineering, Philadelphia University, Amman, Jordan
6Folkhälsan Research Center and Medicum, University of Helsinki, Helsinki, Finland
7Biocenter Oulu, University of Oulu, Oulu, Finland
8PKU & Genetic Consultation Clinic, Amman, Jordan
9Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland
10Northern Finland Laboratory Centre NordLab, Oulu University Hospital, Oulu, Finland
11Clinic for Children and Adolescents, Oulu University Hospital, Oulu, Finland
12Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe202102013390
Language: English
Published: John Wiley & Sons, 2020
Publish Date: 2021-08-10
Description:

Abstract

TATA‐box binding protein associated factor, RNA polymerase I subunit C (TAF1C) is a component of selectivity factor 1 belonging to RNA polymerase I (Pol I) transcription machinery. We report two unrelated patients with homozygous TAF1C missense variants and an early onset neurological phenotype with severe global developmental delay. Clinical features included lack of speech and ambulation and epilepsy. MRI of the brain demonstrated widespread cerebral atrophy and frontal periventricular white matter hyperintensity. The phenotype resembled that of a previously described variant of UBTF, which encodes another transcription factor of Pol I. TAF1C variants were located in two conserved amino acid positions and were predicted to be deleterious. In patient‐derived fibroblasts, TAF1C mRNA and protein expression levels were substantially reduced compared with healthy controls. We propose that the variants impairing TAF1C expression are likely pathogenic and relate to a novel neurological disease. This study expands the disease spectrum related to Pol I transcription machinery, associating the TAF1C missense variants with a severe neurological phenotype for the first time.

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Series: Clinical genetics
ISSN: 0009-9163
ISSN-E: 1399-0004
ISSN-L: 0009-9163
Volume: 98
Issue: 5
Pages: 493 - 498
DOI: 10.1111/cge.13827
OADOI: https://oadoi.org/10.1111/cge.13827
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
3111 Biomedicine
3123 Gynaecology and paediatrics
Subjects:
Funding: This work was supported by the Arvo and Lea Ylppö Foundation, Stiftelsen Alma och K. A. Snellman Säätiö, and Oulun Lääketieteellinen Tutkimussäätiö. RH is supported by the Newton Fund (MR/N027302/1), the Medical Research Council (UK) (MR/N025431/1), the Wellcome Investigator Award (109915/Z/15/Z), the Lily Foundation UK and the Evelyn Trust. RH is a member of the European Reference Network for Rare Neuromuscular Diseases EURO‐NMD.
Copyright information: © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Knuutinen, O, Pyle, A, Suo‐Palosaari, M, et al. Homozygous TAF1C variants are associated with a novel childhood‐onset neurological phenotype. Clin Genet. 2020; 98: 493– 498, which has been published in final form at https://doi.org/10.1111/cge.13827. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.