Academy of Medical Sciences of I.R. Iran Archives of Iranian Medicine 1029-2977 22 12 2019 12 01 Homozygous Mutation in TWNK Cases Ataxia, Sensorineural Hearing Loss and Optic Nerve Atrophy 728 730 EN Faezeh Jamali Hamid Ghaedi Abbas Tafakhori Elham Alehabib Marjan Chapi Narsis Daftarian Hossein Darvish Javad Jamshidi Journal Article 2018 08 16 2019 09 28 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.