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Arch Iran Med. 2019;22(12): 728-730.
PMID: 31823625
Scopus ID: 85076339219
  Abstract View: 1644
  PDF Download: 882

Case Report

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

Faezeh Jamali 1, Hamid Ghaedi 1, Abbas Tafakhori 2, Elham Alehabib 3, Marjan Chapi 1, Narsis Daftarian 4, Hossein Darvish 5*, Javad Jamshidi 6,7

1 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
3 Student Research Committee, Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
6 Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
7 Neuroscience Research Australia, Sydney, NSW, Australia
*Corresponding Author: Email: darvish_mg@yahoo.com

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.

Cite this article as: Jamali F, Ghaedi H, Tafakhori A, Alehabib E, Chapi M, Daftarian N, et al. Homozygous mutation in TWNK cases ataxia, sensorineural hearing loss and optic nerve atrophy. Arch Iran Med. 2019;22(12):728–730.
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Submitted: 16 Aug 2018
Accepted: 28 Sep 2019
ePublished: 01 Dec 2019
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