| 11555109 | Mitochondrial ND3 G10398A mutation: a biomarker for breast cancer. | Yu Y, etal., Genet Mol Res. 2015 Dec 21;14(4):17426-31. doi: 10.4238/2015.December.21.12. | Mitochondrial DNA mutations have been found to play important roles in carcinogenesis. The most common G10398A mutation, a non-conservative amino acid substitution from Thr to Ala, seems to be involved in the tumorigenesis of breast cancer. Results from studies concerning this mutation remain inconc lusive. In the current study, we first took clinical and molecular datasets from case-control studies to determine the association between the G10398A mutation and breast cancer. We further used the Phylotree to determine the haplogroups of this mutation. The frequencies of this mutation in 500 unrelated healthy controls were also screened. We found that this mutation is very common in the human population, and may be a polymorph. | 26782384 | 2015-10-01 |
| 11071157 | A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality. | Crimi M, etal., Pediatr Res. 2004 May;55(5):842-6. Epub 2004 Feb 5. | We describe a new mitochondrial DNA mutation in a male infant who presented clinical and magnetic resonance imaging features of Leigh syndrome and died at the age of 9 mo. The patient's development was reportedly normal in the first months of life. At the age of 5 mo, he presented severe generalized hypotonia, nystagmus, and absent eye contact. Laboratory examination showed increased lactate and pyruvate in both serum and cerebrospinal fluid. Brain magnetic resonance imaging revealed multiple necrotic lesions in the basal ganglia, brain stem, and thalamus. Muscle histopathology was unremarkable, whereas respiratory chain enzyme analysis revealed a severe complex I deficiency. The patient died after an acidotic coma at age 9 mo. Sequence analysis of the entire mtDNA disclosed a new T10158C mutation with variable tissue heteroplasm (muscle: 83%; blood: 48%). The mutation was undetectable in the blood of his unaffected mother. The transition changes a serine residue into a proline, in a highly conserved region of the NADH dehydrogenase subunit 3 (ND3). This is the first description of a mitochondrial ND3 gene in Leigh syndrome with early lethality. | 14764913 | 2004-04-01 |
| 11071295 | Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3. | Leshinsky-Silver E, etal., Mol Genet Metab. 2010 May;100(1):65-70. doi: 10.1016/j.ymgme.2010.02.002. Epub 2010 Feb 10. | Leigh syndrome can be caused by defects in both nuclear and mitochondrial genes involved in energy metabolism. Recently, an increasing number of mutations in mitochondrial DNA encoding regions, especially in NADH dehydrogenase (respiratory chain complex I) subunits, have been reported as causative o f early onset Leigh syndrome. We describe a patient whose fetal brain ultrasound demonstrated periventricular pseudocyst suggestive of a possible mitochondrial disorder who presented postnatally with Leigh syndrome. A muscle biopsy demonstrated a partial decrease in complex I and pyruvate dehydrogenase (PDH-E1 alpha) activity. Sequencing of the PDH-E1 alpha gene did not reveal any mutation. Sequencing of the mtDNA revealed a novel heteroplasmic G10254A (D66N) mutation in the ND3 gene. This change results in a substitution of aspartic acid to asparagine in a highly conserved domain of the ND3 subunit. The mutation could not be detected in the mother's blood or urine sediment. Blue native gel electrophoresis of muscle mitochondria revealed a normal size, albeit a decreased level of complex I. The G10254A substitution in the mtDNA-ND3 gene is another cause of maternally inherited Leigh syndrome. This case demonstrates that periventricular pseudocysts may be the initial in utero presentation in patients with mitochondrial disorders. We emphasize the importance of screening the mtDNA in pediatric patients as the first step in molecular diagnosis of Leigh syndrome. | 20202874 | 2010-04-01 |
| 5508703 | Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia. | Wang K, etal., Neurogenetics. 2009 Oct;10(4):337-45. Epub 2009 May 21. | Leber hereditary optic neuropathy and dystonia (LDYT) is a mitochondrial disorder associated with variable combinations of vision loss and progressive generalized dystonia. LDYT is a unique oxidative phosphorylation disorder caused by mutations in mitochondrial ND6 or ND4 gene. In this paper, we des cribe a Chinese family with 18 LDYT patients. The comprehensive nucleotide sequence analysis of the entire mitochondrial genome using resequencing microarray revealed a mutation (mtND3*10197A (m.10197G>A)) substituting a threonine for a highly conserved alanine at codon 47 of MTND3 on the background of haplogroup D4b. Quantitative analysis of the heteroplasmy of the mutation revealed a homoplasmy in the leukocytes of all the affected individuals on the maternal side. This is the first description of the ND3 mutation causing LDYT. The mtND3*10197A (m.10197G>A) mutation has recently been described in French and Korean patients with Leigh syndrome. These findings suggest that the clinical presentations associated with the mtND3*10197A (m.10197G>A) mutation (ND3) are much wider, encompassing those of LDYT and Leigh syndrome. | 19458970 | 2009-10-01 |
| 11066530 | Rapid identification of a novel complex I MT-ND3 m.10134C>A mutation in a Leigh syndrome patient. | Miller DK, etal., PLoS One. 2014 Aug 12;9(8):e104879. doi: 10.1371/journal.pone.0104879. eCollection 2014. | Leigh syndrome (LS) is a rare progressive multi-system neurodegenerative disorder, the genetics of which is frequently difficult to resolve. Rapid determination of the genetic etiology of LS in a 5-year-old girl facilitated inclusion in Edison Pharmaceutical's phase 2B clinical trial of EPI-743. SNP -arrays and high-coverage whole exome sequencing were performed on the proband, both parents and three unaffected siblings. Subsequent multi-tissue targeted high-depth mitochondrial sequencing was performed using custom long-range PCR amplicons. Tissue-specific mutant load was also assessed by qPCR. Complex I was interrogated by spectrophotometric enzyme assays and Western Blot. No putatively causal mutations were identified in nuclear-encoded genes. Analysis of low-coverage off-target mitochondrial reads revealed a previously unreported mitochondrial mutation in the proband in MT-ND3 (m.10134C>A, p.Q26K), a Complex I mitochondrial gene previously associated with LS. Targeted investigations demonstrated that this mutation was 1% heteroplasmic in the mother's blood and homoplasmic in the proband's blood, fibroblasts, liver and muscle. Enzyme assays revealed decreased Complex I activity. The identification of this novel LS MT-ND3 variant, the genomics of which was accomplished in less than 3.5 weeks, indicates that rapid genomic approaches may prove useful in time-sensitive cases with an unresolved genetic diagnosis. | 25118196 | 1000-04-01 |
| 5507824 | De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency. | McFarland R, etal., Ann Neurol. 2004 Jan;55(1):58-64. | Both nuclear and mitochondrial DNA mutations can cause energy generation disorders. Respiratory chain complex I deficiency is the most common energy generation disorder and a frequent cause of infantile mitochondrial encephalopathies such as Leigh's disease and lethal infantile mitochondrial disease . Most such cases have been assumed to be caused by nuclear gene defects, but recently an increasing number have been shown to be caused by mutations in the mitochondrially encoded complex I subunit genes ND4, ND5, and ND6. We report the first four cases of infantile mitochondrial encephalopathies caused by mutations in the ND3 subunit gene. Three unrelated children have the same novel heteroplasmic mutation (T10158C), only the second mutation reported in ND3, and one has the previously identified T10191C mutation. Both mutations cause disproportionately greater reductions in enzyme activity than in the amount of fully assembled complex I, suggesting the ND3 subunit plays an unknown but important role in electron transport, proton pumping, or ubiquinone binding. Three cases appear to have a de novo mutation, with no mutation detected in maternal relatives. Mitochondrial DNA disease may be considerably more prevalent in the pediatric population than currently predicted and should be considered in patients with infantile mitochondrial encephalopathies and complex I deficiency. | 14705112 | 2004-10-01 |
| 11073474 | Fulminant neurological deterioration in a neonate with Leigh syndrome due to a maternally transmitted missense mutation in the mitochondrial ND3 gene. | Leshinsky-Silver E, etal., Biochem Biophys Res Commun. 2005 Aug 26;334(2):582-7. | Leigh syndrome can result from both nuclear and mitochondrial DNA defects. Mutations in complex V genes of the respiratory chain were considered until recently as the most frequent cause for mitochondrial inherited Leigh syndrome, while gene defects in complex I were related to recessive Leigh syndr ome. Recently few reports of mutations in the mitochondrial-encoded complex I subunit genes causing Leigh syndrome have been reported. We describe a 1-month-old baby who acutely deteriorated, with abrupt onset of brainstem dysfunction, due to basal ganglia lesions extending to the brainstem. A muscle biopsy demonstrated complex I deficiency. Subsequent analysis of the mitochondrial genome revealed a homoplastic T10191C mutation in the ND3 gene (in blood and muscle), resulting in a substitution of serine to proline. Hair root analysis revealed a 50% mutant load, reflecting heteroplasmy in early embryonic stages. The mutation was also detected in his mother (5%). Western blot analysis revealed a decrease of the 20 kDa subunit (likely ND6) and of the 30 kDa subunit (NDUFA9), which is probably due to instability attributed to the inability to form subcomplexes with ND3. This is the first description of infantile Leigh syndrome due to a maternally transmitted T10191C substitution in ND3 and not due to a de novo mutation. This mutation is age and tissue dependent and therefore may not be amenable to prenatal testing. | 16023078 | 2005-04-01 |
| 2302314 | Identification of the mitochondrial NADH dehydrogenase subunit 3 (ND3) as a thyroid hormone regulated gene by whole genome PCR analysis. | Iglesias T, etal., Biochem Biophys Res Commun. 1995 May 25;210(3):995-1000. | We previously described a modification of the whole genome PCR method which allowed us to characterize several genes whose expression is regulated by thyroid hormone in the mouse liver. Following this procedure, we now report the identification of the mitochondrial NADH dehydrogenase subunit 3 (... (more) n style='font-weight:700;'>ND3) gene as target of thyroid hormone. ND3 gene expression is regulated by thyroid hormone in rat brain and heart. Sequencing and electrophoretic mobility shift assays confirmed the presence of a thyroid hormone receptor (TR)/c-erbA specific binding site in the mitochondrial ND3 gene. Hypothyroidism decreases ND3 mRNA levels in several brain areas such as cortex and hippocampus during the early postnatal development. In line with the recent findings showing the presence of TR/c-erbA alpha and beta proteins inside the mitochondria, our results suggest the possibility of direct transcriptional regulation of mitochondrial genes by thyroid hormone. | 7763274 | 1995-12-01 |
