A novel heteroplasmic mitochondrial DNA mutation, A8890G, in a patient with juvenile-onset metabolic syndrome: A case report

YE, WEI; CHEN, SAIHUI; JIN, SHENG; LU, JIANXIN

doi:10.3892/mmr.2013.1616

Cited by 12Mitochondrial Function and PathologyMetabolism and Genetic DisordersGenomics and Rare Diseases

A novel heteroplasmic mitochondrial DNA mutation, A8890G, in a patient with juvenile-onset metabolic syndrome: A case report

Open access

YE, WEI, CHEN, SAIHUI, JIN, SHENG, LU, JIANXIN·2013·Molecular Medicine Reports

DOI 10.3892/mmr.2013.1616

Open this paper in CoChat — free account Open PDF

Abstract

Metabolic syndrome (MS) is a complex disorder characterized by a group of metabolic abnormalities. In the present study, the case of an 18‑year‑old male who presented with MS characteristics with central obesity (overweight and a waist circumference of 95 cm) and dyslipidemia (high TG, low HDL levels and low apoA‑I/apoB‑100) was reported. The patient's family has maternally inherited diabetes and a number of the patient's maternal relatives present MS features. For the investigation of the mitochondrial DNA variants in the patient and the patient's family, genomic DNA of all the family members were extracted from peripheral blood using routine methods. Amplification of mitochondrial DNA in 24 overlapping fragments by PCR, direct sequencing and denaturing high‑performance liquid chromatography was utilized for genetic analysis. Sequences were compared to the reference sequence to identify variants. Bioinformatic methods and databases were used to analyze conservation of the variants and to predict the protein secondary structure. With the exception of the patient, five relatives were diagnosed with MS. Moreover, 5 of the 8 family members had been diagnosed with diabetes, hearing loss and mild kidney impairment according to serum biochemical analysis. Further molecular genetic analysis indicated that the MS‑associated variant T16189C was detected in this family. Notably, a heteroplasmic mutation A8890G was detected in the patient in the mitochondrial ATP6 gene, which codes the ATP synthase subunit 6 (ATPase6). A8890G changed the highly conserved ATPase6 Lys122 into Glu122 in the mitochondrial inner membrane. However, this mutation was not detected in other family members. In conclusion, the mutation A8890G may affect the function of ATPase 6 and the production of ATP, thus contributing to juvenile‑onset MS. It was not detected in other family members possibly due to the mitochondrial genetic segregation or production of a new germline mutation in the juvenile‑onset patient.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.3892/mmr.2013.1616

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

A juvenile patient with a metabolic syndrome phenotype carried the A8890G mtDNA mutation.
“In addition, the A8890G mtDNA mutation was found in a juvenile patient with the metabolic syndrome phenotype131.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [131]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Sequence and organization of the human mitochondrial genome
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., et al. (1981) · Nature · doi:10.1038/290457a0 · Cited by 9,640 · see citing works
The metabolic syndrome—a new worldwide definition
Alberti, K. G. M., Zimmet, P., & Shaw, J. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67402-8 · Cited by 9,352 · see citing works
The metabolic syndrome in children and adolescents ? an IDF consensus report
Zimmet, P., Alberti, K. G. M., Kaufman, F., Tajima, N., Silink, M., Arslanian, S., Wong, G., Bennett, P., Shaw, J., Caprio, S., et al. (2007) · Pediatric Diabetes · doi:10.1111/j.1399-5448.2007.00271.x · Cited by 2,013 · see citing works
Waist circumference and not body mass index explains obesity-related health risk
Janssen, I., Katzmarzyk, P. T., & Ross, R. (2004) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/79.3.379 · Cited by 2,009 · see citing works
Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress
Yakes, F. M., & Van Houten, B. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.2.514 · Cited by 1,854 · see citing works
Molecular Architecture of the Rotary Motor in ATP Synthase
Stock, D., Leslie, A. G. W., & Walker, J. E. (1999) · Science · doi:10.1126/science.286.5445.1700 · Cited by 1,271 · see citing works
Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness
van den Ouweland, J. M. W., Lemkes, H. H. P. J., Ruitenbeek, W., Sandkuijl, L. A., de Vijlder, M. F., Struyvenberg, P. A. A., van de Kamp, J. J. P., & Maassen, J. A. (1992) · Nature Genetics · doi:10.1038/ng0892-368 · Cited by 1,127 · see citing works
Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003-2006.
Ervin, R. B. (2009) · PubMed · Cited by 1,003 · see citing works
The metabolic syndrome in children and adolescents
Zimmet, P., Alberti, G., KAUFMAN, F. R., Tajima, N., Silink, M., Arslanian, S. A., Wong, G., Bennett, P. H., Shaw, J. E., & Caprio, S. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60958-1 · Cited by 963 · see citing works
Prevalence of the metabolic syndrome and overweight among adults in China
Gu, D., Reynolds, K., Wu, X., Chen, J., Duan, X., Reynolds, R. F., Whelton, P. K., & He, J. (2005) · The Lancet · doi:10.1016/s0140-6736(05)66375-1 · Cited by 917 · see citing works
Increasing Prevalence of Metabolic Syndrome in Korea
Lim, S. K., Shin, H., Song, J. H., Kwak, S. H., Kang, S. M., Yoon, J. W., Choi, S. H., Cho, S., Park, K. S., Lee, H. K., et al. (2011) · Diabetes Care · doi:10.2337/dc10-2109 · Cited by 585 · see citing works
Automating the identification of DNA variations using quality-based fluorescence re-sequencing: analysis of the human mitochondrial genome
Rieder, M. J. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.4.967 · Cited by 510 · see citing works
Heteroplasmic mtDNA mutation (T----G) at 8993 can cause Leigh disease when the percentage of abnormal mtDNA is high.
Tatuch, Y., Christodoulou, J., Feigenbaum, A., Clarke, J. T. R., Wherret, J., Smith, C., Rudd, N., Petrova-Benedict, R., & Robinson, B. H. (1992) · PubMed · Cited by 483 · see citing works
Mitochondrial Diabetes
Maassen, J. A., ‘t Hart, L. M., van Essen, E., Heine, R. J., Nijpels, G., Jahangir Tafrechi, R. S., Raap, A. K., Janssen, G. M. C., & Lemkes, H. H. P. J. (2004) · Diabetes · doi:10.2337/diabetes.53.2007.s103 · Cited by 439 · see citing works
A Cluster of Metabolic Defects Caused by Mutation in a Mitochondrial tRNA
Wilson, F. H., Hariri, A., Farhi, A., Zhao, H., Petersen, K. F., Toka, H. R., Nelson-Williams, C. J., Raja, K. M., Kashgarian, M. J., Shulman, G. I., et al. (2004) · Science · doi:10.1126/science.1102521 · Cited by 355 · see citing works
Modification Defect at Anticodon Wobble Nucleotide of Mitochondrial tRNAsLeu(UUR) with Pathogenic Mutations of Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes
Yasukawa, T., Suzuki, T., Suzuki, T., Ueda, T., Ohta, S., & Watanabe, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.6.4251 · Cited by 268 · see citing works
Defective Mitochondrial Biogenesis
Nisoli, E., Clementi, E., Carruba, M. O., & Moncada, S. (2007) · Circulation Research · doi:10.1161/01.res.0000259591.97107.6c · Cited by 224 · see citing works
The mtDNA T8993G (NARP) mutation results in an impairment of oxidative phosphorylation that can be improved by antioxidants
Mattiazzi, M. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh103 · Cited by 221 · see citing works
The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome-associated human mitochondrial tRNALeu(UUR) mutation causes aminoacylation deficiency and concomitant reduced association of mRNA with ribosomes
Chomyn, A., Enriquez, J. A., Micol, V., Fernandez-Silva, P., & Attardi, G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m908734199 · Cited by 197 · see citing works
Mitochondrial DNA Is Required for Regulation of Glucose-stimulated Insulin Secretion in a Mouse Pancreatic Beta Cell Line, MIN6
Soejima, A., Inoue, K., Takai, D., Kaneko, M., Ishihara, H., Oka, Y., & Hayashi, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.42.26194 · Cited by 149 · see citing works
The mitochondrial DNA mutation at 8993 associated with NARP slows the rate of ATP synthesis in isolated lymphoblast mitochondria.
Tatuch, Y., & Robinson, B. H. (1993) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1006/bbrc.1993.1390 · Cited by 142 · see citing works
Studies of the Pro12Ala Polymorphism of the PPAR-γ Gene in the Danish MONICA Cohort: Homozygosity of the Ala Allele Confers a Decreased Risk of the Insulin Resistance Syndrome
Frederiksen, L., Brødbæk, K., Fenger, M., Jørgensen, T., Borch‐Johnsen, K., Madsbad, S., & Urhammer, S. A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.8.8732 · Cited by 118 · see citing works
Inefficient coupling between proton transport and ATP synthesis may be the pathogenic mechanism for NARP and Leigh syndrome resulting from the T8993G mutation in mtDNA
Sgarbi, G., Baracca, A., Lenaz, G., Valentino, M. L., Carelli, V., & Solaini, G. (2006) · Biochemical Journal · doi:10.1042/bj20051748 · Cited by 117 · see citing works
Biochemical phenotypes associated with the mitochondrial ATP6 gene mutations at nt8993
Baracca, A., Sgarbi, G., Mattiazzi, M., Casalena, G., Pagnotta, E., Valentino, M. L., Moggio, M. G., Lenaz, G., Carelli, V., & Solaini, G. (2007) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2007.05.005 · Cited by 116 · see citing works
Interleukin-6 serum levels and genotypes influence the risk for myocardial infarction
Bennet, A. (2003) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2003.08.029 · Cited by 113 · see citing works
Nutrigenetics, Plasma Lipids, and Cardiovascular Risk
Ordovás, J. M. (2006) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2006.04.016 · Cited by 94 · see citing works
Mitochondrial Gene Mutations in the tRNALeu(UUR) Region and Diabetes: Prevalence and Clinical Phenotypes in Japan
Ohkubo, K., Yamano, A., Nagashima, M., Mori, Y., Anzai, K., Akehi, Y., Nomiyama, R., Asano, T., Urae, A., & Ono, J. (2001) · Clinical Chemistry · doi:10.1093/clinchem/47.9.1641 · Cited by 92 · see citing works
Mitochondrial DNA segregation in the developing embryo
Shoubridge, E. A. (2000) · Human Reproduction · doi:10.1093/humrep/15.suppl_2.229 · Cited by 90 · see citing works
The Diabetes-associated 3243 Mutation in the Mitochondrial tRNALeu(UUR) Gene Causes Severe Mitochondrial Dysfunction without a Strong Decrease in Protein Synthesis Rate
Janssen, G. M. C., Maassen, J. A., & van den Ouweland, J. M. W. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.29744 · Cited by 86 · see citing works
The Mitochondrial T16189C Polymorphism Is Associated with Coronary Artery Disease in Middle European Populations
Mueller, E. E., Eder, W., Ebner, S., Schwaiger, E., Santic, D., Kreindl, T., Stanger, O., Paulweber, B., Iglseder, B., Oberkofler, H., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016455 · Cited by 85 · see citing works
The Pathogenic A3243G Mutation in Human Mitochondrial tRNALeu(UUR) Decreases the Efficiency of Aminoacylation
Park, H. J., Davidson, E., & King, M. P. (2002) · Biochemistry · doi:10.1021/bi026882r · Cited by 79 · see citing works
Impairment of tRNA processing by point mutations in mitochondrial tRNA<sup>Leu(UUR)</sup> associated with mitochondrial diseases
Rossmanith, W., & Karwan, R. M. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00928-4 · Cited by 73 · see citing works
Why Young Adults Hold the Key to Assessing the Obesity Epidemic in Children
Lee, J. M. (2008) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.162.7.682 · Cited by 73 · see citing works
Energy-driven subunit rotation at the interface between subunit a and the c oligomer in the F O sector of Escherichia coli ATP synthase
Hutcheon, M. L., Duncan, T. M., Ngai, H., & Cross, R. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151236798 · Cited by 64 · see citing works
Heterogeneous clinical presentation of the mtDNA NARP/T8993G mutation
Santorelli, F. M., Tanji, K., Shanske, S., et al. (1997) · Neurology · doi:10.1212/wnl.49.1.270 · Cited by 53 · see citing works
Variation in the Lamin A/C Gene
Steinle, N., Kazlauskaite, R., Imumorin, I. G., Hsueh, W., Pollin, T. I., O’Connell, J. R., Mitchell, B. D., & Shuldiner, A. R. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000136384.53705.c9 · Cited by 52 · see citing works
Regulation and Role of the Mitochondrial Transcription Factor in the Diabetic Rat Heart
Nishio, Y., Kanazawa, A., Nagai, Y., Inagaki, H., & Kashiwagi, A. (2004) · Springer eBooks · doi:10.1007/978-3-662-41088-2_9 · Cited by 44 · see citing works
Metabolic Syndrome in Children and Adolescents
Arya, A. (2007) · Advances in Pediatrics · doi:10.5005/jp/books/10034_83 · Cited by 39 · see citing works
T16189C mitochondrial DNA variant is associated with metabolic syndrome in Caucasian subjects
Palmieri, V. O., Rasmo, D. D., Signorile, A., et al. (2010) · Nutrition · doi:10.1016/j.nut.2010.08.016 · Cited by 37 · see citing works
Regulation and Role of the Mitochondrial Transcription Factor in the Diabetic Rat Heart
Nishio, Y., Kanazawa, A., Nagai, Y., Inagaki, H., & Kashiwagi, A. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1293.009 · Cited by 34 · see citing works
A common mitochondrial polymorphism 10398A>G is associated metabolic syndrome in a Chinese population
Juo, S. H., Lu, M., Bai, R., Liao, Y., Trieu, R. B., Yu, M., & Wong, L. C. (2010) · Mitochondrion · doi:10.1016/j.mito.2010.01.001 · Cited by 29 · see citing works
Prevalence of the Metabolic Syndrome among rural original adults in NingXia, China
Yi, Z., Jin, J., Xiu-ying, L., et al. (2010) · BMC Public Health · doi:10.1186/1471-2458-10-140 · Cited by 27 · see citing works
An LMNA variant is associated with dyslipidemia and insulin resistance in the Japanese
Murase, Y., Yagi, K., Katsuda, Y., et al. (2002) · Metabolism · doi:10.1053/meta.2002.34030 · Cited by 22 · see citing works
De Novo mtDNA nt 8993 (T→G) Mutation Resulting in Leigh Syndrome
Takahashi, S., Makita, Y., Oki, J., et al. (1998) · The American Journal of Human Genetics · doi:10.1086/301751 · Cited by 16 · see citing works
UK classification of cannabis: is a change needed and why?
Degenhardt, L. J., Hall, W., Roxburgh, A., et al. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61655-9 · Cited by 4 · see citing works

Flagged first, then by citations

Sorted by citations

Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990 · see citing works
ATP Synthase Diseases of Mitochondrial Genetic Origin
Dautant, A., Meier, T., Hahn, A., Tribouillard-Tanvier, D., di Rago, J.-P., & Kucharczyk, R. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00329 · Cited by 127 · see citing works
Germline and somatic mtDNA mutation spectrum of rheumatoid arthritis patients in the Taizhou area, China
Du, J., Yu, S., Wang, D., Chen, S., Chen, S., Zheng, Y., Wang, N., Chen, S., Li, J., & Shen, B. (2020) · Rheumatology · doi:10.1093/rheumatology/keaa063 · Cited by 17 · see citing works
Self-citation

Segregation of mitochondrial DNA (mtDNA) in human oocytes and in animal models of mtDNA disease: clinical implications
Poulton, J. (2002) · Reproduction · doi:10.1530/reprod/123.6.751 · Cited by 4 · see citing works
Assisted Reproductive Technologies to Prevent Transmission of Mitochondrial DNA Disease
Hyslop, L. (2019) · Springer eBooks · doi:10.1007/978-3-319-43011-9_72
Segregation of mitochondrial DNA (mtDNA) in human oocytes and in animal models of mtDNA disease: clinical implications
Poulton, J., & Marchington, D. R. (2002) · Reproduction · doi:10.1530/rep.0.1230751 · Cited by 72 · see citing works
Mitochondrial heteroplasmy beyond the oocyte bottleneck
van den Ameele, J., Li, A. Y. Z., Ma, H., & Chinnery, P. F. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.10.001 · Cited by 76 · see citing works
The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both?
Chinnery, P. F., Thorburn, D. R., Samuels, D. C., White, S. L., Dahl, H.-H. M., Turnbull, D. M., Lightowlers, R. N., & Howell, N. (2000) · Trends in Genetics · doi:10.1016/s0168-9525(00)02120-x · Cited by 253 · see citing works

Authors: YE, W., CHEN, S., JIN, S., & LU, J.
Affiliations: Wenzhou Medical University (CN)
ORCID: YE, WEI
JIN, SHENG
Venue: Molecular Medicine Reports
Publisher: Spandidos Publications
Published: 2013-08-06
Volume: 8
Issue: 4
Pages: 1060-1066
ISSN: 1791-2997 (ISSN-L)
1791-3004
DOI: 10.3892/mmr.2013.1616
OpenAlex: W2080400903
Cited by: 12
References: 45
Citations by year: 2023: 1 · 2022: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2015: 2
FWCI: 0.30
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Molecular Medicine Reports (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords: metabolic syndrome, mitochondrial DNA mutations, heteroplasmy, ATP6 gene, ATP synthase subunit 6, abdominal obesity, dyslipidemia, germline mutations
MeSH terms: Adolescent, Adult, Aged, 80 and over, Base Sequence, DNA, Mitochondrial, Female, Humans, Male, Middle Aged, Pedigree, Point Mutation, Sequence Analysis, DNA, Genetic Predisposition to Disease, Metabolic Syndrome, Mitochondrial Proton-Translocating ATPases, Genetic Association Studies

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

A novel heteroplasmic mitochondrial DNA mutation, A8890G, in a patient with juvenile-onset metabolic syndrome: A case report

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks