MicroRNA expression profile of a Malaysian Bajau family with familial mitochondrial neurogastrointestinal encephalomyopathy

Abstract

ABSTRACT. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare, autosomal recessive disorder associated with mutations in the thymidine phosphorylase (TYMP) gene. The main objective of this study was to characterize the genetic profiles of the deceased proband's family members (N = 4) using DNA sequencing and to determine miRNA deregulation in MNGIE using miRNA microarray profiling and bioinformatic analysis. We found that the genetic profile of the younger sister showed similar TYMP gene mutations as that of the proband with the exception of a heterozygous mutation in exon 10. The miRNA microarray revealed 55 significantly up-regulated and 65 significantly down-regulated miRNAs. These miRNAs have been implicated in various mitochondrial dynamics such as energy metabolism, Krebs cycle, mitochondria-associated apoptosis, and mitophagy. In conclusion, we demonstrate that blood miRNAs are deregulated in the pathogenesis of MNGIE and these changes may have therapeutic implications. Further experimental studies will be required to elucidate the functional miRNA-mRNA interactions in MNGIE.

Circulating miRNAs as Biomarkers for Mitochondrial Neuro-Gastrointestinal Encephalomyopathy

“…In this study we reported a significant dysregulation of 82 miRNAs in the serum of patients compared to age and sex matched healthy controls, however, a critical limitation of this study was the small number of patients recruited (n =5). Previous to this feasibility study, Yong et al reported a miRNA profiling study in a single patient with MNGIE and a cohort of heterozygous family members, using a microarray-based screening [36].…”

Discovery profiling and bioinformatics analysis of serum microRNA in Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE)

“…The only other study which has investigated the involvement of miRNAs in MNGIE is that of Yong et al [29] (2015) who conducted a miRNA expression profile in whole blood of a single patient with MNGIE and a cohort of heterozygous family members [29]. However, no quality control checks were conducted to assess haemolysis, which has been shown to alter miRNA profiles [30].…”

Differential diagnosis of POLG related disorders: What to keep in mind when multiorgan system is involved?

“…Onset is usually between the irst and ifth decade in about 60% of individuals and symptoms begin before 20 years. The diagnosis of MNGIE disease can be established in a proband by detection of one of the following: biallelic pathogenic variants in TYMP; markedly reduced levels of thymidine phosphorylase enzyme activity; and elevated plasma concentrations of thymidine and deoxy-uridine [35][36][37][38]. h) TK2-related mtDNA depletion syndrome: Mitochondrial myopathy with mtDNA depletion is caused by pathogenic variants in TK2.…”