Case Report ARTICLE
A Novel TTC19 Mutation in a Patient with Neurological, Psychological and Gastrointestinal Impairment
- 1Independent researcher, Iran
- 2Neonatal Research Center, Shiraz University of Medical Sciences, Iran
- 3Italian Institute for Genomic Medicine (IIGM), Italy
- 4INSERM U964 Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), France
- 5Center for Therapeutic Innovation, Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, United States
Mitochondrial complex III deficiency, nuclear type 2 is an autosomal-recessive disorder caused by mutations in TTC19 gene. TTC19 is involved in the preservation of mitochondrial complex III, which is responsible for transfer of electrons from reduced coenzyme Q to cytochrome C and thus, contributes to the formation of electrochemical potential and subsequent ATP generation. Mutations in TTC19 have been found to be associated with a wide range of neurological and psychological manifestations. Herein, we report on a 15-year-old boy born from first-degree cousin parents, who initially presented with psychiatric symptoms. He subsequently developed progressive ataxia, spastic paraparesis with involvement of caudate bodies and lentiform nuclei with cerebellar atrophy. Eventually, the patient developed gastrointestinal involvement. Using whole-exome sequencing (WES), we identified a novel homozygous frameshift mutation in TTC19 gene in the patient (NM_017775.3, c.581delG: p.Arg194Asnfs*16). Advanced genetic sequencing technologies developed in recent years have not only facilitated identification of novel disease genes, but also allowed revelations about novel phenotypes associated with mutations in the genes already linked with other clinical features. Our findings expanded the clinical features of TTC19 mutation to potentially include gastrointestinal involvement. Further functional studies are needed to elucidate the underlying pathophysiological mechanisms.
Keywords: Mitochondrial Diseases, Mitochondrial Encephalomyopathies, TTC19, Mitochondrial Complex III Deficiency, Neurodegenerative Diseases
Received: 05 Apr 2019;
Accepted: 15 Aug 2019.
Edited by:Jie Shen, Brigham and Women's Hospital, Harvard Medical School, United States
Reviewed by:Filippo M. Santorelli, Fondazione Stella Maris (IRCCS), Italy
Georgia Xiromerisiou, Faculty of Medicine, School of Health Sciences, University of Thessaly, Greece
Copyright: © 2019 Habibzadeh, Inaloo, Silawi, Dastsooz, Farazi Fard, Sadeghipour, Faghihi, Rezaeian, Yavarian, Böhm and Faghihi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Mohammad ali Faghihi, Center for Therapeutic Innovation, Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, United States, firstname.lastname@example.org