Document Detail


Prenatal diagnosis of myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome: contribution to understanding mitochondrial DNA segregation during human embryofetal development.
MedLine Citation:
PMID:  16690729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Myopathy, encephalopathy, lactic acidosis, and stroke-like (MELAS) syndrome, a maternally inherited disorder that is among the most common mitochondrial DNA (mtDNA) diseases, is usually associated with the m.3242A>G mutation of the mitochondrial tRNA(leu) gene. Very few data are available with respect to prenatal diagnosis of this serious disease. The rate of mutant versus wild-type mtDNA (heteroplasmy) in fetal DNA is indeed considered to be a poor indicator of postnatal outcome. MATERIALS AND METHODS: Taking advantage of a novel semi-quantitative polymerase chain reaction test for m.3243A>G mutant load assessment, we carried out nine prenatal diagnoses in five unrelated women, using two different fetal tissues (chorionic villi v amniocytes) sampled at two or three different stages of pregnancy. RESULTS: Two of the five women, although not carrying m.3243A>G in blood or extra-blood tissues, were, however, considered at risk for transmission of the mutation, as they were closely related to MELAS-affected individuals. The absence of 3243A>G in the blood of first degree relatives was associated with no mutated mtDNA in the cardiovascular system (CVS) or amniocytes, and their three children are healthy, with a follow-up of 3 months-3 years. Among the six fetuses from the three carrier women, three were shown to be homoplasmic (0% mutant load), the remaining three being heteroplasmic, with a mutant load ranging from 23% to 63%. The fetal mutant load was fairly stable at two or three different stages of pregnancy in CVS and amniocytes. Although pregnancy was terminated in the case of the fetus with a 63% mutant load, all other children are healthy with a follow-up of 3 months-6 years. CONCLUSION: These data suggest that a prenatal diagnosis for MELAS syndrome might be helpful for at-risk families.
Authors:
C Bouchet; J Steffann; J Corcos; S Monnot; V Paquis; A Rötig; S Lebon; P Levy; G Royer; I Giurgea; N Gigarel; A Benachi; Y Dumez; A Munnich; J P Bonnefont
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-11
Journal Detail:
Title:  Journal of medical genetics     Volume:  43     ISSN:  1468-6244     ISO Abbreviation:  J. Med. Genet.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-18     Completed Date:  2006-12-04     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2985087R     Medline TA:  J Med Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  788-92     Citation Subset:  IM    
Affiliation:
Department of Genetics, Hôpital Necker-Enfants Malades, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Acidosis, Lactic / diagnosis,  embryology,  genetics
Adolescent
Adult
Child
Child, Preschool
DNA Mutational Analysis
DNA, Mitochondrial / diagnostic use*
Family
Female
Fetal Development / genetics*
Genes, Mitochondrial / genetics*
Humans
Infant
MELAS Syndrome / diagnosis*,  embryology,  genetics
Male
Mitochondrial Encephalomyopathies / diagnosis,  embryology,  genetics
Muscular Diseases / diagnosis,  embryology,  genetics
Pedigree
Polymerase Chain Reaction
Pregnancy
Prenatal Diagnosis / methods*
RNA, Transfer, Leu / genetics
Stroke / diagnosis,  embryology,  genetics
Chemical
Reg. No./Substance:
0/DNA, Mitochondrial; 0/RNA, Transfer, Leu
Comments/Corrections

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