• Faezeh Jamali, Hamid Ghaedi, Abbas Tafakhori, Elham Alehabib, Marjan Chapi, Narsis Daftarian, Hossein Darvish, and Javad Jamshidi.
• Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
• Arch Iran Med. 2019 Dec 1; 22 (12): 728-730.

AbstractThe 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.

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