For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
49
views
18
references
 Top references
cited by
151
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      117
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness.

      Author(s):
      Publication date:
      Journal: Nature genetics
      Keywords: Base Sequence, Cells, Cultured, Child, DNA, Mitochondrial, genetics, isolation & purification, Deafness, complications, Diabetes Mellitus, Type 2, Female, HeLa Cells, Heterozygote Detection, Homozygote, Humans, Male, Middle Aged, Molecular Sequence Data, Muscles, metabolism, Oligodeoxyribonucleotides, Pedigree, Point Mutation, Polymorphism, Restriction Fragment Length, RNA, RNA, Transfer, Leu, Restriction Mapping

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Non-insulin-dependent (type II) diabetes mellitus (NIDDM) is characterized by hyperglycaemia and insulin resistance, and affects nearly 5% of the general population. Inherited factors are important for its development, but the genes involved are unknown. We have identified a large pedigree in which NIDDM, in combination with a sensorineural hearing loss, is maternally inherited. The maternal inheritance and the observed decrease in mitochondrial enzyme activities of the respiratory chain indicate a genetic defect in the mitochondrial DNA. An A to G transition was identified at nucleotide 3,243, a conserved position in the mitochondrial gene for tRNA(Leu)(UUR). This mutation cosegregates with the disease in this family and is absent in controls, and indicates that a point mutation in mitochondrial DNA is a pathogenetic factor for NIDDM.

          Related collections

          Most cited references18

          • Record: found
          • Abstract: found
          • Article: not found

          Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation.

          J M Shoffner, M Lott, A Lezza … (1990)
          An A to G transition mutation at nucleotide pair 8344 in human mitochondrial DNA (mtDNA) has been identified as the cause of MERRF. The mutation alters the T psi C loop of the tRNA(Lys) gene and creates a CviJI restriction site, providing a simple molecular diagnostic test for the disease. This mutation was present in three independent MERRF pedigrees and absent in 75 controls, altered a conserved nucleotide, and was heteroplasmic. All MERRF patients and their less-affected maternal relatives had between 2% and 27% wild-type mtDNAs and showed an age-related association between genotype and phenotype. This suggests that a small percentage of normal mtDNAs has a large protective effect on phenotype. This mutation provides molecular confirmation that some forms of epilepsy are the result of deficiencies in mitochondrial energy production.
          Article 0 comments Cited 176 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion.

            I Trounce, Julia Polak, S H Ballinger … (1992)
            Diabetes mellitus (DM) is one of the most common chronic disorders of children and adults. Several reports have suggested an increased incidence of maternal transmission in some forms of DM. Therefore, we tested a pedigree with maternally transmitted DM and deafness for mitochondrial DNA mutations and discovered a 10.4 kilobase (kb) mtDNA deletion. This deletion is unique because it is maternally inherited, removes the light strand origin (OL) of mtDNA replication, inhibits mitochondrial protein synthesis, and is not associated with the hallmarks of mtDNA deletion syndromes. This discovery demonstrates that DM can be caused by mtDNA mutations and suggests that some of the heterogeneity of this disease results from the novel features of mtDNA genetics.
            Article 0 comments Cited 62 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              MELAS: clinical features, biochemistry, and molecular genetics.

              Maria Nathália C. M. Moraes, S Shanske, G Silvestri … (1992)
              We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, and 50 mitochondrial disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in the transfer RNA(Leu(UUR)) gene of mitochondrial DNA. We found a high concordance between clinical diagnosis of MELAS and transfer RNA(Leu(UUR)) mutation, which was present in 21 of the 23 patients with MELAS, all 11 oligosymptomatic and 12 of 14 asymptomatic relatives, but in only five of 50 patients without MELAS. The proportion of mutant genomes in muscle ranged from 56 to 95% and was significantly higher in the patients with MELAS than in their oligosymptomatic or asymptomatic relatives. In subjects in whom both muscle and blood were studied, the percentage of mutations was significantly lower in blood and was not detected in three of 12 asymptomatic relatives. The activities of complexes I + III, II + III, and IV were decreased in muscle biopsies harboring the mutation, but there was no clear correlation between percentage of mutant mitochondrial DNAs and severity of the biochemical defect.
              Article 0 comments Cited 52 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                PubMed ID:: 1284550
                DOI:: 10.1038/ng0892-368

                ScienceOpen disciplines: Chemistry
                Keywords: Base Sequence,Cells, Cultured,Child,DNA, Mitochondrial,genetics,isolation & purification,Deafness,complications,Diabetes Mellitus, Type 2,Female,HeLa Cells,Heterozygote Detection,Homozygote,Humans,Male,Middle Aged,Molecular Sequence Data,Muscles,metabolism,Oligodeoxyribonucleotides,Pedigree,Point Mutation,Polymorphism, Restriction Fragment Length,RNA,RNA, Transfer, Leu,Restriction Mapping
                Data availability:
                ScienceOpen disciplines: Chemistry
                Keywords: Base Sequence, Cells, Cultured, Child, DNA, Mitochondrial, genetics, isolation & purification, Deafness, complications, Diabetes Mellitus, Type 2, Female, HeLa Cells, Heterozygote Detection, Homozygote, Humans, Male, Middle Aged, Molecular Sequence Data, Muscles, metabolism, Oligodeoxyribonucleotides, Pedigree, Point Mutation, Polymorphism, Restriction Fragment Length, RNA, RNA, Transfer, Leu, Restriction Mapping

                Comments

                Comment on this article

                scite_

                Similar content117

                See all similar

                Cited by147

                See all cited by

                Most referenced authors665

                See all reference authors