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MERRF/MELAS overlap syndrome: A double pathogenic mutation in mitochondrial tRNA genes

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Title: MERRF/MELAS overlap syndrome: A double pathogenic mutation in mitochondrial tRNA genes
Authors: Nakamura, Masakazu Browse this author
Yabe, Ichiro Browse this author →KAKEN DB
Sudo, Akira Browse this author
Hosoki, Kana Browse this author
Yaguchi, Hiroaki Browse this author
Saitoh, Shinji Browse this author →KAKEN DB
Sasaki, Hidenao Browse this author →KAKEN DB
Issue Date: 7-Jul-2010
Publisher: BMJ Publishing
Journal Title: Journal of Medical Genetics
Volume: 47
Issue: 10
Start Page: 659
End Page: 664
Publisher DOI: 10.1136/jmg.2009.072058
PMID: 20610441
Abstract: Background : Myoclonic epilepsy with ragged-red fibres (MERRF) and mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are established phenotypes of mitochondrial encephalomyopathy. The m.8356T>C transition in the mitochondrial tRNALys gene is a pathogenic mutations of MERRF. The m.3243A>G transition in the mitochondrial tRNALeu gene is detected in most MELAS patients. Although previous analyses of double mutations in mitochondrial DNA (mtDNA) were useful for discussing their nature, many unsolved questions remain. Objective : To describe the clinical and genetic features of a family with the above mtDNA double-point mutations and discuss the role of double mtDNA mutations in diverse clinical features in the family. Patients and methods : The proband was a 23-year-old woman with MERRF harbouring m.8356T>C and m.3243A>G transitions in mitochondrial tRNA genes. We assessed clinical aspects of her and those of her three relatives and performed mutation analyses on their mtDNA. Results : Phenotypes of the four patients were MERRF, MERRF/MELAS overlap syndrome and asymptomatic carrier. We hypothesise that the course of the phenotype of this family begins with MERRF and is followed by MELAS. This double mutation was heteroplasmic in blood of all four patients but with different rates in each patient, while m.8356T>C appeared homoplasmic and m.3243A>G was heteroplasmic in muscle of the two examined cases. No other mutations were detected in the total mtDNA sequence in this family. Conclusions : This is the first reported case of a double-point mutation in mtDNA, both of which were heteroplasmic and pathogenic for the established phenotypes.
Rights: This article has been accepted for publication in Journal of Medical Genetics (JMG). The definitive copyedited, typeset version [insert complete citation information when available] is available online at : http://jmg.bmj.com
Relation: http://jmg.bmj.com/site/about/unlocked.xhtml
Type: article (author version)
URI: http://hdl.handle.net/2115/44728
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 矢部 一郎

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