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

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http://hdl.handle.net/10138/332971

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Knuutinen , O , Pyle , A , Suo-Palosaari , M , Duff , J , Froukh , T , Lehesjoki , A-E , Kangas , S M , Cassidy , J , Maraqa , L , Keski-Filppula , R , Kokkonen , H , Uusimaa , J , Horvath , R & Vieira , P 2020 , ' Homozygous TAF1C variants are associated with a novel childhood-onset neurological phenotype ' , Clinical Genetics , vol. 98 , no. 5 , pp. 493-498 . https://doi.org/10.1111/cge.13827

Title: Homozygous TAF1C variants are associated with a novel childhood-onset neurological phenotype
Author: Knuutinen, Oula; Pyle, Angela; Suo-Palosaari, Maria; Duff, Jennifer; Froukh, Tawfiq; Lehesjoki, Anna-Elina; Kangas, Salla M.; Cassidy, James; Maraqa, Latifa; Keski-Filppula, Riikka; Kokkonen, Hannaleena; Uusimaa, Johanna; Horvath, Rita; Vieira, Päivi
Contributor: University of Helsinki, University of Helsinki
Date: 2020-11
Language: eng
Number of pages: 6
Belongs to series: Clinical Genetics
ISSN: 0009-9163
URI: http://hdl.handle.net/10138/332971
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 homozygousTAF1Cmissense 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 ofUBTF, which encodes another transcription factor of Pol I.TAF1Cvariants were located in two conserved amino acid positions and were predicted to be deleterious. In patient-derived fibroblasts,TAF1CmRNA and protein expression levels were substantially reduced compared with healthy controls. We propose that the variants impairingTAF1Cexpression are likely pathogenic and relate to a novel neurological disease. This study expands the disease spectrum related to Pol I transcription machinery, associating theTAF1Cmissense variants with a severe neurological phenotype for the first time.
Subject: brain atrophy
infantile spasms
Pol I transcription initiation complex proteins
TATA-binding protein associated factors
ENCEPHALOPATHY
PROTEIN
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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