TY - JOUR
T1 - Primary Hyperoxaluria Type 1: Update and Additional Mutation Analysis of the AGXT Gene
AU - Williams, Emma L.
AU - Acquaviva, Cecile
AU - Amoroso, Antonio
AU - Chevalier, Francoise
AU - Coulter-Mackie, Marion
AU - Monico, Carla G.
AU - Giachino, Daniela
AU - Owen, Tricia
AU - Robbiano, Angela
AU - Salido, Eduardo
AU - Waterham, Hans
AU - Rumsby, Gill
PY - 2009
Y1 - 2009
N2 - Primary hyperoxaluria type 1 (PH1) is an autosomal recessive, inherited disorder of glyoxylate metabolism arising from a deficiency of the alanine: glyoxylate aminotransferase (AGT) enzyme, encoded by the AGXT gene. The disease is manifested by excessive endogenous oxalate production, which leads to impaired renal function and associated morbidity. At least 146 mutations have now been described, 50 of which are newly reported here. The mutations, which occur along the length of the AGXT gene, are predominantly single-nucleotide substitutions (75%), 73 are missense, 19 nonsense, and 18 splice mutations; but 36 major and minor deletions and insertions are also included. There is little association of mutation with ethnicity, the most obvious exception being the p.Ile244Thr mutation, which appears to have North African/Spanish origins. A common, polymorphic variant encoding leucine at codon 11 the so-called minor allele, has significantly lower catalytic activity in vitro, and has a higher frequency in PHI compared to the rest of the population. This polymorphism influences enzyme targeting in the presence of the most common Gly170Arg mutation and potentiates the effect of several other pathological sequence variants. This review discusses the spectrum of AGXT mutations and polymorphisms, their clinical significance, and their diagnostic relevance. Hum Mutat 30, 910-917, 2009. (C) 2009 Wiley-Liss, Inc
AB - Primary hyperoxaluria type 1 (PH1) is an autosomal recessive, inherited disorder of glyoxylate metabolism arising from a deficiency of the alanine: glyoxylate aminotransferase (AGT) enzyme, encoded by the AGXT gene. The disease is manifested by excessive endogenous oxalate production, which leads to impaired renal function and associated morbidity. At least 146 mutations have now been described, 50 of which are newly reported here. The mutations, which occur along the length of the AGXT gene, are predominantly single-nucleotide substitutions (75%), 73 are missense, 19 nonsense, and 18 splice mutations; but 36 major and minor deletions and insertions are also included. There is little association of mutation with ethnicity, the most obvious exception being the p.Ile244Thr mutation, which appears to have North African/Spanish origins. A common, polymorphic variant encoding leucine at codon 11 the so-called minor allele, has significantly lower catalytic activity in vitro, and has a higher frequency in PHI compared to the rest of the population. This polymorphism influences enzyme targeting in the presence of the most common Gly170Arg mutation and potentiates the effect of several other pathological sequence variants. This review discusses the spectrum of AGXT mutations and polymorphisms, their clinical significance, and their diagnostic relevance. Hum Mutat 30, 910-917, 2009. (C) 2009 Wiley-Liss, Inc
U2 - https://doi.org/10.1002/humu.21021
DO - https://doi.org/10.1002/humu.21021
M3 - Article
C2 - 19479957
SN - 1059-7794
VL - 30
SP - 910
EP - 917
JO - Human mutation
JF - Human mutation
IS - 6
ER -