Description:
Arginase (EC
3.5.3.1) catalyzes the last step of the urea cycle. It is present
in 2 forms, specified by separate gene loci, ARG1 and ARG2. The isoform
encoded by ARG1, referred to as the liver isoform, contributes 98
% of the arginase activity in liver but is also present in red cells.
ARG2 encodes the mitochondrial isoform, which predominates in kidney.
Arginase deficiency is an autosomal recessive inborn error of metabolism,
which causes elevated plasma arginine, called argininemia. This disorder
is not typically characterized by rapid-onset hyperammonemia. Affected
individuals develop progressive spasticity and can also develop tremor,
ataxia, and choreoathetosis. Growth is affected. ARG1 is
located at chromosome 6q23. ARG1 contains 8 exons encoding a 322 amino
acid protein.
Reasons for Referral:
-
Confirmation of a clinical diagnosis
- Carrier testing
- Prenatal diagnosis for known familial mutations
Testing Methodology:
The exons and flanking intronic regions of the ARG1 gene
are PCR amplified and sequenced in both the forward and reverse directions.
Blood: EDTA (purple-top)
tubes: Adult: 14
cc; Child: 6 cc; Infant: 2-3 cc
Requisition form must accompany the specimen. To receive forms,
additional information or specimen collection kits, please contact the
laboratory. Please call laboratory for specific requirements for
prenatal testing.
Turnaround Time:Index: 4 weeks
Known Familial Mutation: 2 weeks
Index: 83891, 83904x16, 83898x8,
83912, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891,
83894x2
Forms:
>> Gene
Sequencing Requisition or Mitochondrial
Requisition - Mitochondrial Diagnostic Checklist is included
>> Prenatal
Requisition
References:
1. Haraguchi, Y.; Takiguchi, M.; Amaya,
Y.; Kawamoto, S.; Matsuda, I.; Mori, M.: Molecular cloning and nucleotide
sequence of cDNA for human liver arginase. Proc.
Nat. Acad. Sci. 84:
412-415, 1987.
2. Takiguchi, M.; Haraguchi, Y.; Mori, M.: Human liver-type
arginase gene: structure of the gene and analysis of thepromoterregion.Nucleic
Acids Res. 16: 8789-8802, 1988.
3. Haraguchi, Y.; Aparicio R., J. M.; Takiguchi, M.; Akaboshi,
I.; Yoshino, M.; Mori, M.; Matsuda, I.: Molecular basis of argininemia:
identification of two discrete frame-shift deletions in the liver-type
arginase gene.J.
Clin. Invest. 86: 347-350, 1990.
4. Grody, W. W.; Klein, D.; Dodson, A. E.; Kern, R. M.;
Wissmann, P. B.; Goodman, B. K.; Bassand, P.; Marescau, B.; Kang, S.-S.;
Leonard, J. V.; Cederbaum, S. D.: Molecular genetic study of human arginase
deficiency Am.
J. Hum. Genet. 50: 1281-1290, 1992.
5. Uchino, T.; Haraguchi, Y.; Aparicio, J. M.; Mizutani,
N.; Higashikawa, M.; Naitoh, H.; Mori, M.; Matsuda, I.: Three novel mutations
in the liver-type arginase gene in three unrelated Japanese patients
with argininemia.Am.
J. Hum. Genet. 51: 1406-1412, 1992.
6. Uchino,
T.; Snyderman, S. E.; Lambert, M.; Qureshi, I. A.; Shapira, S. K.; Sansaricq,
C.; Smit, L. M. E.; Jakobs, C.; Matsuda, I.: Molecular basis of phenotypic
variation in patients with argininemia.Hum. Genet. 96:
255-260, 1995.
7. Vockley JG, Goodman BK, Tabor DE, Kern RM, Jenkinson
CP, Grody WW, Cederbaum SD.: Loss of function mutations in conserved
regions of the human arginase I gene. Biochem Mol Med. 59( 1): 44-51,
1996.
8. Cardoso, M. L.; Martins, E.; Vasconcelos, R.; Vilarinho,
L.; Rocha, J.: Identification of a novel R21X mutation in the liver-type
arginase gene (ARG1) in four Portuguese patients with argininemia.Hum.
Mutat. 14: 355-356, 1999.
9. Korman SH, Gutman A, Stemmer E, Kay BS, Ben-Neriah Z,
Zeigler M.: Prenatal diagnosis for arginase deficiency by second-trimester
fetal erythrocyte arginase assay and first-trimester ARG1 mutation analysis.
Prenat Diagn. 24(11):857-60, 2004.
Test Codes:
Index: 3425
Known Familial Mutation: 3426
Prenatal: 3427
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