Abstract Details

Title POLG Mutations in Patients with Mitochondrial Myopathy and Multiple mtDNA Deletions

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) P07 - (-)

Poster/Presentation
Number 025

Objective

Background BACKGROUND: Multiple deletions and depletion of mtDNA are caused by nuclear gene mutations, with autossomal dominant or recessive transmission. The most frequent phenotype is progressive external ophthalmoplegia (PEO). The genes associated with this type of abnormality are ANT1, PEO1 and POLG.

Design/Methods DESIGN/METHODS: We studied 10 independent patients. All of them had muscle biopsy showing ragged red fibers and cytochrome c oxidase negative fibers. Multiple deletions of mtDNA were detected by Southern blotting. The entire coding region of POLG was analyzed by DNA sequencing.

Results RESULTS: Mutations were detected in five patients. One patient had a mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)-like syndrome (absence of leukoencephalopathy) with a compound heterozigous mutation (p.A889T; p.E1143G) with two affected siblings with the same mutation. Two patients had the homozygous mutation p.G848S, with PEO and myopathy, and one with no family history. Two homozygous variations were not previously described (p.Y622S; p.V400M) and were observed in patients with PEO. pY622S was located in a non-conserved region of the gene, while p.V400M was in a conserved region and was not found in 100 controls.

Conclusions CONCLUSIONS: Mutations in POLG were frequent in this group of patients. We found POLG mutations in a patient with MNGIE-like syndrome, which is an uncommon phenotype associated with this gene. The p.V400M variation is probably a novel mutation.

Authors/Disclosures
Celia H. Tengan, MD (Universidade Federal De Sao Paulo) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Ugur Uygunoglu (Cerrahpasa)	Ugur Uygunoglu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Turkey . The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Idec/Gen Pharma of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck-Serono of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanovel of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Genveon of Turkey.
	No disclosure on file
Acary S. Oliveira, MD (UNIFESP - Escuela Paulista De Medicina)	No disclosure on file
Alberto A. Gabbai, MD	No disclosure on file
	No disclosure on file
Beatriz H. Kiyomoto	No disclosure on file

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