Expression signature of the Leigh syndrome French-Canadian type

Bchetnia, Mbarka; Tardif, Jessica; Morin, Charles; Laprise, Catherine

doi:10.1016/j.ymgmr.2022.100847

Cited by 6 publications

(6 citation statements)

References 37 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This family of proteins binds to RNA and regulates transcription. It plays an important role in RNA processing, splicing, stability, editing and translation, mainly manifested in strong inhibitionof autophagy [14] and complex interaction with apoptosis. LRPPRC has been shown to play an important regulatory role in many diseases.…”

Section: Discussionmentioning

confidence: 99%

Screening of key genes for m6A modification differences in childhood sepsis

Hong,

Wu,

2024

Preprint

View full text Add to dashboard Cite

Sepsis in children is a syndrome associated with organ dysfunction caused by immune dysregulation of inflammatory responses in children. According to the latest data, nearly50 million people have been diagnosed with sepsisand nearly10 million have died. M6A methylation has been reported to be associated with sepsis-associated inflammatory response[2],however, the molecular biological mechanism underlying the diagnosis and treatment of m6A related genes in children remains unclear. It provides a new way for clinical incidence prediction and molecular biology diagnosis, and further guides clinical treatment.The GEO database chip dataset GSE66099 was downloaded and annotated by platform files. The m6A related genes were extracted. The data were standardized by R language limma package.181 children with septic shock,18 children with sepsis were selected as sepsis group,47 normal childrenand30 children with common SIRS were selected as control group. The difference of m6A gene expression between control group and sepsis group was analyzed by correlation test. The importance score of m6A-related genes in sepsis was obtained by cross-validation error of random forest tree method, disease-related characteristic genes were screened, the influence of core difference genes on sepsis incidence was analyzed, and nomogram was drawn to predict patient incidence. The number of disease characteristic genes was determined by LASSO model, ROC curve was drawn, and related genes were selected for further analysis. Cluster analysis was performed on sepsis patients according to the expression of biomarkers, and difference and correlation analysis were performed on immune infiltration. Among the first 13 differentially expressed genes, DIGFBP1 and IGFBP2 were up-regulated in sepsis patients, while METTL3, MITTL14, MERTTL16, RBM15, RBM15B, CBLL1, YTHF2, HNRNPC, LRPPRC, ELAVL1 and FTO were down-regulated in sepsis patients. In addition, ROC curve analysis showed that HNRNPC, LRPPRC, FTO andELAVL1 were characteristic genes of the disease. We also identified two m6A genotypes and two differential genotypes. Based on differential gene expression, nine m6A gene expressions were statistically different in a 2-typing pattern, with differences associated with immune infiltration. m6A methylation modification may play a potentially important role in the diagnosis,immune infiltration and treatment of sepsis in children. HNRNPC may be one of the potential molecular markers for predicting sepsis in children. Typing based on m6A gene expression has potential implications for the treatment of sepsis in children.

show abstract

Section: Discussionmentioning

confidence: 99%

Screening of key genes for m6A modification differences in childhood sepsis

Hong,

Wu,

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Wahedi et al performed transcriptome analysis of 113 genes, currently associated with Leigh syndrome, and showed neuronal specificity of target genes, with significant enrichment in hippocampal and somatosensory pyramidal neurons as well as interneurons of the brain [ 70 ]. A previously described, transcriptomic profile analysis of fibroblasts harboring pathogenic variants in the LRPPRC gene, associated with Leigh syndrome, French-Canadian type (MIM #220111), obtained a set of DEGs and identified NDUFA4L2 gene as a target for further functional studies [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of the m.13513G>A Variant on the Functions of the OXPHOS System and Cell Retrograde Signaling

Kidere

Zayakin

Livcane

et al. 2023

CIMB

View full text Add to dashboard Cite

Mitochondria are involved in many vital functions in living cells, including the synthesis of ATP by oxidative phosphorylation (OXPHOS) and regulation of nuclear gene expression through retrograde signaling. Leigh syndrome is a heterogeneous neurological disorder resulting from an isolated complex I deficiency that causes damage to mitochondrial energy production. The pathogenic mitochondrial DNA (mtDNA) variant m.13513G>A has been associated with Leigh syndrome. The present study investigated the effects of this mtDNA variant on the OXPHOS system and cell retrograde signaling. Transmitochondrial cytoplasmic hybrid (cybrid) cell lines harboring 50% and 70% of the m.13513G>A variant were generated and tested along with wild-type (WT) cells. The functionality of the OXPHOS system was evaluated by spectrophotometric assessment of enzyme activity and high-resolution respirometry. Nuclear gene expression was investigated by RNA sequencing and droplet digital PCR. Increasing levels of heteroplasmy were associated with reduced OXPHOS system complex I, IV, and I + III activities, and high-resolution respirometry also showed a complex I defect. Profound changes in transcription levels of nuclear genes were observed in the cell lines harboring the pathogenic mtDNA variant, indicating the physiological processes associated with defective mitochondria.

show abstract

“…Inter-organ communication might also be involved in regulation of mitochondrial function by peroxisome-derived lipids. Recent studies identified decreased serum plasmalogens as biomarkers in Leigh Syndrome French-Canadian variant (LSFC), a monogenic mitochondrial disorder in which a mutation in Leucine-rich PPR-motif-containing protein (Lrpprc), a protein that regulates RNA metabolism in mitochondria and nuclei, causes mitochondrial dysfunction, neurodegeneration, and hepatic lactic acidosis [ 9 , 88 , 89 ]. These findings were recapitulated in a LSFC mouse model with liver-specific knockout of Lrpprc, implying that perturbed hepatic peroxisomal ether lipid synthesis is responsible for the decreased serum plasmalogens in LSFC subjects and possibly some of the associated defects in other tissues, such as the brain, where plasmalogens account for approximately 20% of phospholipids [ 40 ] and are a major component of myelin [ 90 ].…”

Section: Role Of Peroxisome-derived Lipids In Energy-homeostasis and ...mentioning

confidence: 99%