New variants in the TMEM126B gene associated with complex I dehydrogenase deficiency identified in a pediatric patient from southwestern of Colombia

Abstract

Introduction: Complex I deficiency is the most common biochemical defect of the oxidative phosphorylation system, has been associated with pathogenic variants in the TMEM126B gene that codes for the TMEM126B assembly factor at the mitochondrial level and results in a diverse phenotypic presentation such as exercise intolerance, muscle weakness, hyperlactic acidemia, hypertrophic cardiomyopathy and renal tubular acidosis. Objective: To report new variants in the TMEM126B gene identified in a pediatric male patient with complex I deficiency. Materials and Methods: An 11-month-old male patient with a history of congenital hypotonia. He underwent whole exome sequencing + CNV by NGS; the Mutation Taster, UMD-Predictor, POLYPHEN, SIFT, DANN, Human Splicing Finder and Varsome. Finally, a gene interaction network was constructed by the GeneMania program to identify close gene associations. Results: Variants c.222_223del (p.Gln74HisfsTer26) and c.509+61del (p?) were identified in the TMEM126B gene. These variants are not reported in population databases and are not described in the world literature. From the analysis in bioinformatics software, it was concluded that they have probably pathogenic and uncertain significance, respectively. The interaction network showed that TMEM126B is directly related to the TMEM126, DYNC12 and NDUFAF1 gene family. Conclusion: The report of new variants in the TMEM126B gene by using genomic-bioinformatics techniques allows us to broaden the spectrum of genetic variants, especially intronic ones, to contribute to the targeted diagnosis of patients with mitochondrial diseases and to provide individualized care and to make an approach to precision medicine.