Selected Exonic Sequencing of the AGXT Gene Provides a Genetic Diagnosis in 50% of Patients with Primary Hyperoxaluria Type I (Molecular Diagnostics and Genetics) Selected Exonic Sequencing of the AGXT Gene Provides a Genetic Diagnosis in 50% of Patients with Primary Hyperoxaluria Type I (Molecular Diagnostics and Genetics)

Selected Exonic Sequencing of the AGXT Gene Provides a Genetic Diagnosis in 50% of Patients with Primary Hyperoxaluria Type I (Molecular Diagnostics and Genetics‪)‬

Clinical Chemistry 2007, July, 53, 7

    • $5.99
    • $5.99

Publisher Description

Primary hyperoxaluria type 1 (PH1) [1] (OMIM 259900) is an autosomal recessive disorder of glyoxylate metabolism caused by deficiency of alanine:glyoxylate aminotransferase (AGT; EC 2.6.1.44). AGT is a pyridoxine 5'-phosphate-dependent enzyme that is liver specific (1) and usually located within the peroxisome (2). This intracellular location allows efficient removal of potentially toxic glyoxylate via conversion to glycine. In the absence of AGT, glyoxylate accumulates and is converted to oxalate, which is excreted by the kidney and leads to hyperoxaluria. Insoluble calcium oxalate salts crystallize in the kidney, leading to urolithiasis and nephrocalcinosis, thereby decreasing renal function, and ultimately leading to end-stage renal failure and systemic oxalosis if treatment is not initiated (3). AGXT, [2] the gene encoding the AGT protein, comprises 11 exons over 10 kb and maps to chromosome 2q37.3 (4). The cDNA contains an open reading frame of 1179 nucleotides encoding a 392-residue polypeptide that homodimerizes to yield a protein of 86 kDa (5). Wild-type AGT exists as 2 main genetic variants, with either a proline (major allele) or leucine (minor allele) residue at position 11 in the protein sequence (6). The minor AGXT allele has a frequency of 15%-20% in European and North American populations (6) but a much higher frequency, ~50%, among PH1 patients (7). The Leu11 variant has several measurable effects on the properties of recombinant AGT protein expressed in vitro. The Leu11 variant encodes a protein with ~50% of the activity of the more common Pro11 allele, and the Leu11 protein has a decreased dimerization rate at increased temperatures (8). There is also evidence that the presence of Leu11 potentiates the effect of some mutations (8, 9).

GENRE
Science & Nature
RELEASED
2007
1 July
LANGUAGE
EN
English
LENGTH
19
Pages
PUBLISHER
American Association for Clinical Chemistry, Inc.
SELLER
The Gale Group, Inc., a Delaware corporation and an affiliate of Cengage Learning, Inc.
SIZE
220.7
KB

More Books by Clinical Chemistry

Lowering Cutoffs for Initial and Confirmation Testing for Cocaine and Marijuana: Large-Scale Study of Effects on the Rates of Drug-Positive Results (Drug Monitoring and Toxicology) Lowering Cutoffs for Initial and Confirmation Testing for Cocaine and Marijuana: Large-Scale Study of Effects on the Rates of Drug-Positive Results (Drug Monitoring and Toxicology)
1997
Myocardial Infarction Redefined: Role of Cardiac Troponin Testing (Editorial) Myocardial Infarction Redefined: Role of Cardiac Troponin Testing (Editorial)
2001
Distribution of Fasting Plasma Insulin, Free Fatty Acids, And Glucose Concentrations and of Homeostasis Model Assessment of Insulin Resistance in a Representative Sample of Quebec Children and Adolescents (Pediatric Clinical Chemistry) Distribution of Fasting Plasma Insulin, Free Fatty Acids, And Glucose Concentrations and of Homeostasis Model Assessment of Insulin Resistance in a Representative Sample of Quebec Children and Adolescents (Pediatric Clinical Chemistry)
2003
C677T and AI298C Polymorphisms of the Methylenetetrahydrofolate Reductase Gene: Incidence and Effect of Combined Genotypes on Plasma Fasting and Post-Methionine Load Homocysteine in Vascular Disease (Molecular Diagnostics and Genetics) C677T and AI298C Polymorphisms of the Methylenetetrahydrofolate Reductase Gene: Incidence and Effect of Combined Genotypes on Plasma Fasting and Post-Methionine Load Homocysteine in Vascular Disease (Molecular Diagnostics and Genetics)
2001
Acetylcholinesterase Activity and Biogenic Amines in Phenylketonuria (Technical Briefs) Acetylcholinesterase Activity and Biogenic Amines in Phenylketonuria (Technical Briefs)
2002
Homocysteine, 5, 10-Methylenetetrahydrofolate Reductase 677CT Polymorphism, Nutrient Intake, And Incident Cardiovascular Disease in 24 968 Initially Healthy Women (Molecular Diagnostics and Genetics) (Clinical Report) Homocysteine, 5, 10-Methylenetetrahydrofolate Reductase 677CT Polymorphism, Nutrient Intake, And Incident Cardiovascular Disease in 24 968 Initially Healthy Women (Molecular Diagnostics and Genetics) (Clinical Report)
2007