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Homozygous Mutation in Twnk Cases Ataxia, Sensorineural Hearing Loss and Optic Nerve Atrophy Pubmed



Jamali F1 ; Ghaedi H1 ; Tafakhori A2 ; Alehabib E3 ; Chapi M1 ; Daftarian N4 ; Darvish H5 ; Jamshidi J6, 7
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Student Research Committee, Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
  6. 6. Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
  7. 7. Neuroscience Research Australia, NSW, Sydney, Australia

Source: Archives of Iranian medicine Published:2019


Abstract

The TWNK (C10orf2) gene encodes Twinkle, an essential helicase for mtDNA replication. Homozygous mutations in TWNK can lead to mitochondrial DNA depletion syndrome 7 (MTDPS7) that usually manifests as Infantile onset spinocerebellar ataxia (IOSCA). Here, we report a 15-year-old Iranian boy with three main symptoms; ataxia, sensorineural hearing loss and optic nerves atrophy which were accompanied by other symptoms including flexion contracture, dysarthric speech, nystagmus, dystonia and borderline intellectual disability. Whole exome sequencing (WES) revealed a homozygous mutation in his TWNK gene. The mutation was a transversion which replaced a C with A (NM_021830.4 (TWNK):c.874C>A). This nucleotide substitution results in replacing a Threonine with Proline in codon 292 of Twinkle protein (p.Pro292Thr). In silico analyses showed that this amino acid change in Twinkle could be deleterious and disease-causing; therefore, we attribute the symptoms of our patient to this mutation. Our study extended the homozygous mutation spectrum of the TWNK gene that leads to IOSCA. © 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.