Description:
LEIGH SYNDROME; LS
ATP SYNTHASE 6; MTATP6
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Carbohydrate Metabolism |
| Class |
Disorders of the Mitochondrial Genome |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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Other
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Relation to Proband
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proband
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Confirmation
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Molecular characterization before cell line submission to CCR
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a positive result with a primer for Yq11, DYS227. |
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| Gene |
MTATP6 |
| Chromosomal Location |
NA |
| Allelic Variant 1 |
516060.0001; LEIGH SYNDROME |
| Identified Mutation |
LEU156ARG; Holt et al. [Am. J. Hum. Genet. 46: 428 (1990)] found a heteroplasmic T-to-G transversion at nucleotide pair 8993 in a maternal pedigree which resulted in the change of a hydrophobic leucine to a hydrophilic arginine at position 156 in subunit 6 of mitochondrial H(+)-ATPase. The clinical symptoms varied in proportion to the percentage of mutant mtDNAs but the most common clinical presentation included neurogenic muscle weakness, ataxia, and retinitis pigmentosa, leading to the designation of NARP (551500). The insertion of an arginine in the hydrophobic sequence of ATPase 6 probably interferes with the hydrogen ion channel formed by subunits 6 and 9 of the ATPase, thus causing failure of ATP synthesis. Tatuch et al. [Am. J. Hum. Genet. 50: 852 (1992)] and Shoffner et al. [Neurology 42: 2168 (1992)] demonstrated that the nucleotide 8993 mutation can cause Leigh disease. |
| Remarks |
Chronic metabolic acidosis; muscle OXPHOS studies showed marked instability of mitochondrial inner membrane; 3 affected generations in pedigree; heteroplasmic for the MTATP6*NARP8993 [8993T>G; Leu156Arg (L156R)] mutation; approximately 95% of mtDNA is mutant |
| Xia Y, Katz M, Chandramohan D, Bechor E, Podgursky B, Hoxie M, Zhang Q, Chertman W, Kang J, Blue E, Chen J, Schleede J, Slotnick NR, Du X, Boostanfar R, Urcia E, Behr B, Cohen J, Siddiqui N, The first clinical validation of whole-genome screening on standard trophectoderm biopsies of preimplantation embryos F&S reports5:63-71 2023 |
| PubMed ID: 38524212 |
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| Chin RM, Panavas T, Brown JM, Johnson KK, Patient-derived lymphoblastoid cell lines harboring mitochondrial DNA mutations as tool for small molecule drug discovery BMC research notes11:205 2018 |
| PubMed ID: 29587845 |
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| Trounce I, Neill S, Wallace DC, Cytoplasmic transfer of the mtDNA nt 8993 T-->G (ATP6) point mutation associated with Leigh syndrome into mtDNA-less cells demonstrates cosegregation with a decrease in state III respiration and ADP/O ratio. Proc Natl Acad Sci U S A91:8334-8 1994 |
| PubMed ID: 8078883 |
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| Ortiz RG, Newman NJ, Shoffner JM, Kaufman AE, Koontz DA, Wallace DC, Variable retinal and neurologic manifestations in patients harboring the mitochondrial DNA 8993 mutation. Arch Ophthalmol111:1525-30 1993 |
| PubMed ID: 8240109 |
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