Molecular basis of argininemia. Identification of two discrete frame-shift deletions in the liver-type arginase gene.
Argininemia results from a deficiency of arginase (EC 3.5.3.1), the last enzyme of the urea cycle in the liver. We examined the molecular basis for argininemia by constructing a genomic library followed by cloning and DNA sequencing. Discrete mutations were found on two alleles from the patient, a product of a nonconsanguineous marriage. There was a four-base deletion at protein-coding region 262-265 or 263-266 in exon 3 that would lead to a reading-frame shift after amino acid residue 87 and make a new stop codon at residue 132. The other was a one-base deletion at 77 or 78 in exon 2 that would lead to a reading-frame shift after residue 26 and make a stop codon at residue 31. For confirmation, genomic DNAs from the patient and from her parents were amplified by the polymerase chain reaction method. The patient was shown to be a compound heterozygote, inheriting an allele with the four-base deletion from the father and the other allele with the one-base deletion from the mother. These data seem to be the first evidence of a case of argininemia caused by two different deletion mutations.
Haraguchi
Y
Y
Department of Pediatrics, Kumamoto University Medical School, Japan.
Aparicio
J M
JM
Takiguchi
M
M
Akaboshi
I
I
Yoshino
M
M
Mori
M
M
Matsuda
I
I
D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D000595:Amino Acid Sequence; D001119:Arginase / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D005260:Female; D006801:Humans; D020162:Hyperargininemia; D008969:Molecular Sequence Data; D009154:Mutation; D009841:Oligonucleotides; D010375:Pedigree; D016133:Polymerase Chain Reaction
D009841:Oligonucleotides; D001119:Arginase