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Lookup NU author(s): Benjamin Munro, Dr Ana TopfORCiD, Professor Hanns Lochmuller, Professor Rita HorvathORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2020 - IOS Press and the authors. All rights reserved. Background: In 2009, we identified TACO1 as a novel mitochondrial disease gene in a single family, however no second family has been described to confirm the role of TACO1 in mitochondrial disease. Objective: In this report, we describe two independent consanguineous families carrying pathogenic variants in TACO1, confirming the phenotype. Methods: Detailed clinical investigations and whole exome sequencing with haplotype analysis have been performed in several members of the two reported families. Results: Clinical phenotype of the patients confirms the originally reported phenotype of a childhood-onset progressive cerebellar and pyramidal syndrome with optic atrophy and learning difficulties. Brain MRI showed periventricular white matter lesions with multiple cystic defects, suggesting leukoencephalopathy in both patients. One patient carried the previously described homozygous TACO1 variant (p.His158ProfsTer8) and haplotype analysis suggested that this variant is a rare founder mutation. The second patient from another family carried a homozygous novel frame shift variant (p.Cys85PhefsTer15). Conclusions: The identification of two Turkish families with similar characteristic clinical presentation and an additional homozygous nonsense mutation confirms that TACO1 is a human mitochondrial disease gene. Although most patients with this clinical presentation undergo next generation sequencing analysis, screening for selected founder mutations in the Turkish population based on the precise clinical presentation may reduce time and cost of finding the genetic diagnosis even in the era of massively parallel sequencing.
Author(s): Oktay Y, Gungor S, Zeltner L, Wiethoff S, Schols L, Sonmezler E, Yilmaz E, Munro B, Bender B, Kernstock C, Kaemereit S, Liepelt I, Topf A, Yis U, Laurie S, Yaramis A, Zuchner S, Hiz S, Lochmuller H, Schule R, Horvath R
Publication type: Article
Publication status: Published
Journal: Journal of Neuromuscular Diseases
Year: 2020
Volume: 7
Issue: 3
Pages: 301-308
Online publication date: 02/06/2020
Acceptance date: 02/04/2018
Date deposited: 26/07/2021
ISSN (print): 2214-3599
ISSN (electronic): 2214-3602
Publisher: IOS Press
URL: https://doi.org/10.3233/JND-200510
DOI: 10.3233/JND-200510
PubMed id: 32444556
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