DNA-based prenatal diagnosis for severe and variant forms of multiple acyl-CoA dehydrogenation deficiency.
OBJECTIVE
Multiple acyl-CoA dehydrogenation deficiency (MADD) is a clinically heterogeneous disorder of mitochondrial fatty acid, amino acid, and choline oxidation due to mutations in the genes encoding electron transfer flavoprotein (ETF) or ETF ubiquinone oxidoreductase (ETFQO). So far, prenatal diagnosis of MADD has relied mostly on second-trimester biochemical analyses of amniotic fluid or cultured amniocytes. We report here on an alternative DNA-based approach for prenatal diagnosis in pregnancies at risk of MADD.


METHODS
We used our knowledge of the mutational status in three unrelated families with a history of MADD to perform direct sequencing for the familial mutations using genomic DNA isolated from chorionic villus samples (CVS) at gestational week 10 to 11.


RESULTS
Within two days, we were able to carry out accurate DNA-based prenatal testing in one pregnancy at risk of severe MADD, and in two pregnancies at risk of variant forms of MADD.


CONCLUSIONS
This is the first report of DNA-based prenatal diagnosis of MADD. Our molecular approach is suitable for fast and reliable first-trimester prenatal diagnosis in pregnancies at risk of severe and variant forms of MADD.
Olsen
Rikke K J
RK
Research Unit for Molecular Medicine, Aarhus University Hospital and Faculty of Health Sciences, Skejby Sygehus, Aarhus, Denmark. rikke.olsen@mmf.au.dk
Andresen
Brage S
BS
Christensen
Ernst
E
Mandel
Hanna
H
Skovby
Flemming
F
Nielsen
Jens Peter
JP
Knudsen
Inga
I
Vianey-Saban
Christine
C
Simonsen
Henrik
H
Gregersen
Niels
N
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D000328:Adult; D002478:Cells, Cultured; D015193:Chorionic Villi Sampling / Q000379:methods*; D004247:DNA / Q000032:analysis*; D044927:Electron-Transferring Flavoproteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D015203:Reproducibility of Results
D044927:Electron-Transferring Flavoproteins; D007506:Iron-Sulfur Proteins; D004247:DNA; D042964:Acyl-CoA Dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase