A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO) - PubMed (original) (raw)
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A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO)
Andres Berardo et al. Neuromuscul Disord. 2010 Mar.
Abstract
We describe a 62-year-old woman with chronic progressive external ophthalmoplegia (CPEO), multiple lipomas, diabetes mellitus, and a novel mitochondrial DNA (mtDNA) mutation at nucleotide 4302 (4302A>G) of the tRNA(Ile) gene (MTTI). This is the first mutation at position 44 in the variable loop (V loop) of any mitochondrial tRNA. The muscle biopsy revealed 10% ragged-red/ragged-blue fibers and 25% cytochrome c oxidase (COX)-deficient fibers. No deletions or duplications were detected by Southern blot analysis. The 4302A>G transition was present only in the patient's muscle and single-fiber analysis revealed significantly higher levels of the mutation in COX-deficient than in normal fibers. Like tRNA(Leu(UUR)), tRNA(Ile) appears to be a "hot spot" for mtDNA mutations causing CPEO.
Copyright 2010 Elsevier B.V. All rights reserved.
Conflict of interest statement
Conflict of interest
None of the authors has any conflict of interest or financial disclosure to declare.
Figures
Fig. 1
(A) Electropherogram of DNA sequence. Electrophoresed samples were analyzed with Sequence Analysis software (Perkin-Elmer Applied Biosystems). At position 4302 a heteroplasmic adenine to guanine transition is evident (4302A>G). (B) Nucleotide sequence showing inter-species similarity of the tRNAIle gene and the highly conserved base at nt 4302. The mutation in our patient is highlighted with a bold red letter and compared with human, bovine, mouse, Xenopus (X) laevis, Drosophila (D) yakuba. (C) PCR-RFLP analysis. Fragments after digestion with _Dde_I were separated on a 15% non-denaturing acrylamide gel, visualized and quantitated using SYBR Gold® Nucleic Acid Gel Stain (Invitrogen). _Dde_I cuts the wild type into a 95 and a 78 bp fragment, whereas mutant mtDNA was digested into three (58, 37 and 78 bp). Patient’s tissues: M, muscle; B, blood; U, urine; C1, C2 (controls); uncut PCR product. (D) Secondary structure of the human wild type tRNAIle showing the nt. 4302 base pair substitution A-to-G at the variable loop (v loop) region. The red points show previously described mutations associated with CPEO phenotype (position 4267, 4274, 4285, 4298, and 4309).
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