A novel mitochondrial transfer RNA(Asn) mutation causing multiorgan failure.
BACKGROUND
Mitochondrial cytopathies are a heterogeneous group of disorders with a broad spectrum of clinical symptoms.


OBJECTIVE
To characterize a novel mutation in the transfer RNA(Asn) (m.5728A>G) identified in a 13-year-old boy with multiorgan failure.


METHODS
Biochemical and immunocytochemical studies were performed in combination with transmitochondrial cybrid analysis.


METHODS
A university hospital. Molecular and biochemical analyses were performed in collaboration between 2 other university hospitals.


METHODS
Thirteen-year-old boy with multiorgan failure.


RESULTS
In the patient's muscle tissue and cultured skin fibroblasts, a combined deficiency of complexes I and IV was found, using spectrophotometric analysis and activity staining in the gel following blue native polyacrylamide gel electrophoresis. An identical biochemical profile was seen in transmitochondrial cybrids carrying more than 55% mutant mitochondrial DNA.


CONCLUSIONS
These data suggest that the m.5728A>G transition is a pathogenic mutation and is the cause of the respiratory chain dysfunction in the propositus.
Meulemans
Ann
A
Center for Medical Genetics, Dutch-Speaking Free University of Brussels, Laarbeeklaan 101, 1090 Brussels, Belgium. ann.meulemans@vub.ac.be
Seneca
Sara
S
Lagae
Lieven
L
Lissens
Willy
W
De Paepe
Boel
B
Smet
Joél
J
Van Coster
Rudy
R
De Meirleir
Linda
L
D000293:Adolescent; D001216:Asparagine / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D008297:Male; D017240:Mitochondrial Myopathies / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D009102:Multiple Organ Failure / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D012348:RNA, Transfer, Asn / Q000235:genetics*
D004272:DNA, Mitochondrial; D012348:RNA, Transfer, Asn; D001216:Asparagine