scholarly journals POLG mutations in sporadic mitochondrial disorders with multiple mtDNA deletions

2003 ◽  
Vol 22 (6) ◽  
pp. 498-499 ◽  
Author(s):  
Alessio Di Fonzo ◽  
Andreina Bordoni ◽  
Marco Crimi ◽  
Galbiati Sara ◽  
Roberto Del Bo ◽  
...  
Keyword(s):  
Mitochondrial Disorders ◽  
Mtdna Deletions

Primary mitochondrial disorders and diabetes mellitus - two case reports

2018 ◽  
Author(s):  
Lucia Fadiga ◽  
Joana Saraiva ◽  
Diana Oliveira ◽  
Adriana Lages ◽  
Mara Ventura ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Case Reports ◽  
Mitochondrial Disorders

scholarly journals POLRMT mutations impair mitochondrial transcription causing neurological disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Monika Oláhová ◽  
Bradley Peter ◽  
Zsolt Szilagyi ◽  
Hector Diaz-Maldonado ◽  
Meenakshi Singh ◽  
...  
Keyword(s):  
Progressive External Ophthalmoplegia ◽  
Global Developmental Delay ◽  
Disease Mechanism ◽  
Mitochondrial Transcription ◽  
Functional Studies ◽  
Mtdna Deletions ◽  
Molecular Nature ◽  
Important Disease

AbstractWhile >300 disease-causing variants have been identified in the mitochondrial DNA (mtDNA) polymerase γ, no mitochondrial phenotypes have been associated with POLRMT, the RNA polymerase responsible for transcription of the mitochondrial genome. Here, we characterise the clinical and molecular nature of POLRMT variants in eight individuals from seven unrelated families. Patients present with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood; one subject displayed an indolent progressive external ophthalmoplegia phenotype. Massive parallel sequencing of all subjects identifies recessive and dominant variants in the POLRMT gene. Patient fibroblasts have a defect in mitochondrial mRNA synthesis, but no mtDNA deletions or copy number abnormalities. The in vitro characterisation of the recombinant POLRMT mutants reveals variable, but deleterious effects on mitochondrial transcription. Together, our in vivo and in vitro functional studies of POLRMT variants establish defective mitochondrial transcription as an important disease mechanism.

scholarly journals Serum biomarkers in primary mitochondrial disorders

2021 ◽  
Author(s):  
Kristin N Varhaug ◽  
Omar Hikmat ◽  
Hanne Linda Nakkestad ◽  
Christian A Vedeler ◽  
Laurence A Bindoff
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mitochondrial Disease ◽  
Central Nervous System Involvement ◽  
Mitochondrial Disorders ◽  
Serum Biomarkers ◽  
Fibroblast Growth Factor 21 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mitochondrial Dna Deletion ◽  
Muscle Involvement

Abstract The aim of this study was to explore the utility of the serum biomarkers neurofilament light chain (NF-L), fibroblast growth factor 21 (FGF-21) and growth and differentiation factor 15 (GDF-15) in diagnosing primary mitochondrial disorders. We measured serum NF-L, FGF-21 and GDF-15 in 26 patients with a genetically proven mitochondrial disease. FGF-21 and GDF-15 were measured by enzyme-linked immunosorbent assay and NF-L with the Simoa assay. NF-L was highest in patients with multisystemic involvement that included the central nervous system such as those with the m.3242A>G mutation. Mean NF-L was also highest in patients with epilepsy versus those without (49.74 pg/ml versus 19.7 pg/ml (p = 0.015)), while FGF-21 and GDF-15 levels were highest in patients with prominent myopathy, such as those with single mitochondrial DNA deletion. Our results suggest that the combination of NF-L, FGF-21 and GDF-15 is useful in the diagnostic evaluation of mitochondrial disease. GDF-15 and FGF-21 identify those with muscle involvement while NF-L is a clear marker for central nervous system involvement independent of underlying mitochondrial pathology. Levels of NF-L appear to correlate with the degree of ongoing damage suggesting, therefore, that monitoring NF-L levels may provide prognostic information and a way of monitoring disease activity.

scholarly journals Mitochondrial Syndromes Revisited

2021 ◽  
Vol 10 (6) ◽  
pp. 1249
Author(s):  
Daniele Orsucci ◽  
Elena Caldarazzo Ienco ◽  
Andrea Rossi ◽  
Gabriele Siciliano ◽  
Michelangelo Mancuso
Keyword(s):  
Clinical Trials ◽  
Genetic Basis ◽  
Phenotypic Variability ◽  
Mitochondrial Diseases ◽  
Genetic Alterations ◽  
Mitochondrial Disorders ◽  
Single Mutation ◽  
Multicenter Studies ◽  
Future Studies ◽  
Clinical Syndromes

In the last ten years, the knowledge of the genetic basis of mitochondrial diseases has significantly advanced. However, the vast phenotypic variability linked to mitochondrial disorders and the peculiar characteristics of their genetics make mitochondrial disorders a complex group of disorders. Although specific genetic alterations have been associated with some syndromic presentations, the genotype–phenotype relationship in mitochondrial disorders is complex (a single mutation can cause several clinical syndromes, while different genetic alterations can cause similar phenotypes). This review will revisit the most common syndromic pictures of mitochondrial disorders, from a clinical rather than a molecular perspective. We believe that the new phenotype definitions implemented by recent large multicenter studies, and revised here, may contribute to a more homogeneous patient categorization, which will be useful in future studies on natural history and clinical trials.

scholarly journals In vivo biodistribution study of TAT-L-Sco2 fusion protein, developed as protein therapeutic for mitochondrial disorders attributed to SCO2 mutations

2020 ◽  
Vol 25 ◽  
pp. 100683
Author(s):  
Georgios C. Kaiafas ◽  
Dionysia Papagiannopoulou ◽  
Αndroulla N. Miliotou ◽  
Anastasia S. Tsingotjidou ◽  
Parthenopi C. Chalkidou ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Mitochondrial Disorders ◽  
Biodistribution Study ◽  
In Vivo Biodistribution ◽  
Protein Therapeutic
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