A novel composition of two heterozygous GFM1 mutations in a Chinese child with epilepsy and mental retardation

Abstract

Mitochondria are the energy factories of eukaryotic cells, which contain thousands of proteins that maintain their specific functions. These proteins are encoded by mitochondrial DNA and the nuclear genome. Pathogenic mutations in these mitochondrial genes can cause multiple serious diseases (Scheffer et al., 2017; Thompson et al., 2020). Mitochondrial DNA encodes its own mRNA, rRNA, and tRNA, to synthesize some of the proteins it needs. Proteins encoded by mitochondrial DNA are involved in the composition of oxidative phosphorylation system complexes, so any gene mutation that affects the replication, transcription, and translation of mitochondrial DNA may cause oxidative phosphorylation deficiency (de Laat, Rodenburg, & Smeitink, 2014). Mitochondrial translation is crucial for maintaining

Dysfunctional mitochondrial translation and combined oxidative phosphorylation deficiency in a mouse model of hepatoencephalopathy due to Gfm1 mutations

“…As observed in other mitochondrial diseases, COXPD1 presents a rather variable clinical phenotype, with some patients rapidly progressing in fatal clinical courses during infancy, 6,7,9,10,12,13,17,19 and others having more stable clinical course and longer survival 8,10–12,15–18 12 .…”

“…Interestingly, there are also reports of a few patients with OXPHOS defects in liver but no hepatic symptoms. 17 As observed in other mitochondrial diseases, COXPD1 presents a rather variable clinical phenotype, with some patients rapidly progressing in fatal clinical courses during infancy, 6,7,9,10,12,13,17,19 and others having more stable clinical course and longer survival. 8,[10][11][12][15][16][17][18] The reasons accounting for the variable phenotype are unknown, although it has been proposed that the protein domain where the mutation is located could determine the severity of the disease.…”

“…Other common clinical traits are feeding difficulties, dystonia, hyper-or hypotonia, West syndrome, brain MRI abnormalities, and liver failure. 3,[6][7][8][9][10][11][12][13][14][15][16][17][18][19] Disease progression is rapid, and many patients die within the first few years of life, sometimes during the perinatal period. The low number of patients described thus far makes it difficult to identify any correlations between genotype and clinical outcome, although some authors have proposed that the mutation localization in the protein could account for the disease severity.…”

“…COXPD1 is an autosomal recessive disease characterized by early‐onset severe encephalopathy coupled with increased lactate levels. Other common clinical traits are feeding difficulties, dystonia, hyper‐ or hypotonia, West syndrome, brain MRI abnormalities, and liver failure 3,6–19 . Disease progression is rapid, and many patients die within the first few years of life, sometimes during the perinatal period.…”

Mitochondrial Protein Translation: Emerging Roles and Clinical Significance in Disease

“…A p.Cys1576Thr mutation in exon 13 of GFM1 resulted in a premature stop codon at amino acid position 526 ( Coenen et al, 2004 ; Su and Wang, 2020 ). WES revealed a novel composition of two heterozygous mutations of GFM1 in a Chinese child with epilepsy and mental retardation ( You et al, 2020 ). In recent years, nine unrelated children were found to carry GFM1 mutation.…”