Faezeh Jamali
1, Hamid Ghaedi
1, Abbas Tafakhori
2, Elham Alehabib
3, Marjan Chapi
1, Narsis Daftarian
4, Hossein Darvish
5*, Javad Jamshidi
6,71 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
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.