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Query: UMLS:C0751651 (mitochondrial disease)
 1,844 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complex I deficiency is a frequent cause of mitochondrial disease as it accounts for one third of these disorders. By genotyping several putative disease loci using microsatellite markers we were able to describe a new NDUFS7 mutation in a consanguineous family with Leigh syndrome and isolated complex I deficiency. This mutation lies in the first intron of the NDUFS7 gene (c.17-1167 C>G) and creates a strong donor splice site resulting in the generation of a cryptic exon. This mutation is predicted to result in a shortened mutant protein of 41 instead of 213 amino acids containing only the first five amino acids of the normal protein. Analysis of the assembly state of the respiratory chain complexes under native condition revealed a marked decrease of fully assembled complex I while the quantity of the other complexes was not altered. These results report the first intronic NDUFS7 gene mutation and demonstrate the crucial role of NDUFS7 in the biogenesis of complex I.
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PMID:A novel mutation of the NDUFS7 gene leads to activation of a cryptic exon and impaired assembly of mitochondrial complex I in a patient with Leigh syndrome. 1760 71

The unicellular slime mould Dictyostelium discoideum is a valuable eukaryotic model organism in the study of mitochondrial biology and disease. As a member of the Amoebozoa, a sister clade to the animals and fungi, Dictyostelium mitochondrial biology shares commonalities with these organisms, but also exhibits some features of plants. As such it has made significant contributions to the study of eukaryotic mitochondrial biology. This review provides an overview of the advances in mitochondrial biology made by the study of Dictyostelium and examines several examples where Dictyostelium has and will contribute to the understanding of mitochondrial disease. The study of Dictyostelium's mitochondrial biology has contributed to the understanding of mitochondrial genetics, transcription, protein import, respiration, morphology and trafficking, and the role of mitochondria in cellular differentiation. Dictyostelium is also proving to be a versatile model organism in the study both of classical mitochondrial disease e.g. Leigh syndrome, and in mitochondria-associated neurodegenerative diseases like Parkinson's disease. The study of mitochondrial diseases presents a unique challenge due to the cryptic nature of their genotype-phenotype relationship. The use of Dictyostelium can contribute to resolving this problem by providing a genetically tractable, haploid eukaryotic organism with a suite of readily characterised phenotype readouts of cellular signalling pathways. Dictyostelium has provided insight into the signalling pathways involved in multiple neurodegenerative diseases and will continue to provide a significant contribution to the understanding of mitochondrial biology and disease.
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PMID:The Dictyostelium model for mitochondrial biology and disease. 3184 Jul 87

The diagnosis of Mendelian disorders following uninformative exome and genome sequencing remains a challenging and often unmet need. Following uninformative exome and genome sequencing of a family quartet including two siblings with suspected mitochondrial disorder, RNA sequencing (RNAseq) was pursued in one sibling. Long-read amplicon sequencing was used to determine and quantify transcript structure. Immunoblotting studies and quantitative proteomics were performed to demonstrate functional impact. Differential expression analysis of RNAseq data identified significantly decreased expression of the mitochondrial OXPHOS Complex I subunit NDUFB10 associated with a cryptic exon in intron 1 of NDUFB10, that included an in-frame stop codon. The cryptic exon contained a rare intronic variant that was homozygous in both affected siblings. Immunoblot and quantitative proteomic analysis of fibroblasts revealed decreased abundance of Complex I subunits, providing evidence of isolated Complex I deficiency. Through multiomic analysis we present data implicating a deep intronic variant in NDUFB10 as the cause of mitochondrial disease in two individuals, providing further support of the gene-disease association. This study highlights the importance of transcriptomic and proteomic analyses as complementary diagnostic tools in patients undergoing genome-wide diagnostic evaluation.
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PMID:Multiomic analysis elucidates Complex I deficiency caused by a deep intronic variant in NDUFB10. 3316 36