A novel mutation in the AGXT gene causing primary hyperoxaluria type I: genotype–phenotype correlation

Abstract

Primary hyperoxaluria type I (PH1) is an autosomal recessive metabolic disorder caused by inherited mutations in the AGXT gene encoding liver peroxisomal alanine : glyoxylate aminotransferase (AGT) which is deficient or mistargeted to mitochondria. PH1 shows considerable phenotypic and genotypic heterogeneity. The incidence and severity of PH1 varies in different geographic regions. DNA samples of the affected members from two unrelated Tunisian families were tested by amplifying and sequencing each of the AGXT exons and intron-exon junctions. We identified a novel frameshift mutation in the AGXT gene, the c.406_410dupACTGC resulting in a truncated protein (p.Gln137Hisfs*19). It is found in homozygous state in two nonconsanguineous unrelated families from Tunisia. These molecular findings provide genotype/phenotype correlations in the intrafamilial phenotypic and permit accurate carrier detection, and prenatal diagnosis. The novel p.Gln137Hisfs*19 mutation detected in our study extend the spectrum of known AGXT gene mutations in Tunisia.

Clinical analysis of 13 children with primary hyperoxaluria type 1

“…The pathogenicity of c.190A > T needs to be further verified by the studies of structure and function of the encoded protein. PH1 is a highly heterogeneous disease of clinical phenotype and genotype [ 14 , 15 ]. In addition, no clear correlation between genotype and phenotype has been found thus far.…”

Non-Coding RNAs in Kidney Stones

“…PH type I (PH1) is one of the most severe hyperoxaluric diseases leading to urolithiasis, nephrocalcinosis, and end-stage renal disease. Due to mutations in alanine-glyoxylate aminotransferase (AGXT) encoding alanine-glyoxylate aminotransferase (AGT), which regulates the final step of glyoxylate metabolism [47], PH1 has long been considered a monogenic disorder. However, recent reports have shown significant genotype-phenotype heterogeneity in patients with PH1, and many patients without AGXT mutations still exhibit PH1-related phenotypes [48].…”