Document Detail


Chronic progressive ophthalmoplegia with large-scale mtDNA rearrangement: can we predict progression?
MedLine Citation:
PMID:  17439982     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The prognosis of chronic progressive ophthalmoplegia with large-scale mitochondrial DNA (mtDNA) may strikingly vary from mild slowly progressive myopathy to severe multi-organ involvement. Evaluation of the disease course at the beginning of the disease is reputed impossible. To address the existence of predictive prognostic clues of these diseases, we classified 69 patients with chronic progressive ophthalmoplegia and large size mtDNA deletion into two groups according to the presence of manifestations from brain, inner ear or retina. These manifestations were present in 29 patients (CPEO/+N group) and absent in 40 patients (CPEO/-N group). We retrospectively established the clinical history of the patients and characterized their genetic alteration (amount of residual normal mtDNA molecules, site, size and percentage of the mtDNA deletion in 116 DNA samples from muscle, blood, urinary and buccal cells). In both clinical groups, the disease was progressive and heart conduction defects were frequent. We show that the CPEO/+N phenotype segregated with severe prognosis in term of rate of progression, multi-organs involvement and rate of survival. Age at onset appeared a predictive factor. The risk to develop a CPEO/+N phenotype was high when onset was before 9 years of age and low when onset was after 20 years of age. The presence and proportion of the mtDNA deletion in blood was also significantly associated with the CPEO/+N phenotype. This study is the first to establish the natural history of chronic ophthalmoplegia with mtDNA deletion in a large series of patients and to look for parameters potentially predictive of the patients' clinical course.
Authors:
Karine Auré; Hélène Ogier de Baulny; Pascal Laforêt; Claude Jardel; Bruno Eymard; Anne Lombès
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-17
Journal Detail:
Title:  Brain : a journal of neurology     Volume:  130     ISSN:  1460-2156     ISO Abbreviation:  Brain     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-25     Completed Date:  2007-06-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372537     Medline TA:  Brain     Country:  England    
Other Details:
Languages:  eng     Pagination:  1516-24     Citation Subset:  AIM; IM    
Affiliation:
Inserm, U582, Paris F-75013, France.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Age of Onset
Child
Child, Preschool
DNA, Mitochondrial / blood,  genetics*
Disease Progression
Follow-Up Studies
Gene Deletion
Gene Rearrangement*
Humans
Kearns-Sayre Syndrome / genetics
Middle Aged
Ophthalmoplegia, Chronic Progressive External / genetics*
Prognosis
Retrospective Studies
Risk Factors
Chemical
Reg. No./Substance:
0/DNA, Mitochondrial

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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