-transparent.png){kind=logo}
Short-chain acyl-CoA dehydrogenase (SCAD) is a homotetrameric mitochondrial flavoenzyme that catalyzes the initial reaction in short-chain fatty acid beta-oxidation. Defects in the SCAD enzyme are associated with failure to thrive, often with neuromuscular dysfunction and elevated urinary excretion of ethylmalonic acid (EMA). To define the genetic basis of SCAD deficiency and ethylmalonic aciduria in patients, we have determined the sequence of the complete coding portion of the human SCAD gene (ACADS) and all of the intron-exon boundaries. The SCAD gene is approximately 13 kb in length and consists of 10 exons. Four polymorphic sites have previously been detected by sequencing of cDNA from fibroblasts of patients excreting elevated amounts of EMA. Three of these polymorphisms (321T/C, 990C/T, 1260G/C) are silent variants, while a 625G/A polymorphism results in an amino acid replacement and has been shown to be associated with ethylmalonic aciduria. From analysis of 18 unrelated Danish families, we show that the four SCAD gene polymorphisms constitute five allelic variants of the SCAD gene, and that the 625A variant together with the less frequent variant form of the three other polymorphisms (321C, 990T, 1260C) constitutes an allelic variant with a frequency of 22% in the general Danish population. Using fluorescence in-situ hybridization, we confirm the localization of the human SCAD gene to the distal part of Chromosome (Chr) 12 and suggest that the SCAD gene is a single-copy gene. The evolutionary relationship between SCAD and five other members of the acyl-CoA dehydrogenase family was investigated by two independent approaches that gave similar phylogenetic trees.
M J Corydon, and
B S Andresen, and
P Bross, and
M Kjeldsen, and
P H Andreasen, and
H Eiberg, and
S Kølvraa, and
N Gregersen
January 1992,
Biochemistry,
M J Corydon, and
B S Andresen, and
P Bross, and
M Kjeldsen, and
P H Andreasen, and
H Eiberg, and
S Kølvraa, and
N Gregersen
September 1998,
Mammalian genome : official journal of the International Mammalian Genome Society,
M J Corydon, and
B S Andresen, and
P Bross, and
M Kjeldsen, and
P H Andreasen, and
H Eiberg, and
S Kølvraa, and
N Gregersen
April 2002,
Nihon rinsho. Japanese journal of clinical medicine,
M J Corydon, and
B S Andresen, and
P Bross, and
M Kjeldsen, and
P H Andreasen, and
H Eiberg, and
S Kølvraa, and
N Gregersen
January 1990,
Progress in clinical and biological research,
M J Corydon, and
B S Andresen, and
P Bross, and
M Kjeldsen, and
P H Andreasen, and
H Eiberg, and
S Kølvraa, and
N Gregersen
January 2001,
Ryoikibetsu shokogun shirizu,
M J Corydon, and
B S Andresen, and
P Bross, and
M Kjeldsen, and
P H Andreasen, and
H Eiberg, and
S Kølvraa, and
N Gregersen
January 1998,
Ryoikibetsu shokogun shirizu,
M J Corydon, and
B S Andresen, and
P Bross, and
M Kjeldsen, and
P H Andreasen, and
H Eiberg, and
S Kølvraa, and
N Gregersen
April 1996,
Mammalian genome : official journal of the International Mammalian Genome Society,
M J Corydon, and
B S Andresen, and
P Bross, and
M Kjeldsen, and
P H Andreasen, and
H Eiberg, and
S Kølvraa, and
N Gregersen
April 1988,
Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme,
M J Corydon, and
B S Andresen, and
P Bross, and
M Kjeldsen, and
P H Andreasen, and
H Eiberg, and
S Kølvraa, and
N Gregersen
March 1993,
Genomics,
M J Corydon, and
B S Andresen, and
P Bross, and
M Kjeldsen, and
P H Andreasen, and
H Eiberg, and
S Kølvraa, and
N Gregersen
January 1990,
Progress in clinical and biological research,
