title: Identification of a novel AGXT gene mutation in primary hyperoxaluria after kidney transplantation failure.
abstract: Primary hyperoxaluria is a genetic disorder in glyoxylate metabolism that leads to systemic overproduction of oxalate. Functional deficiency of alanine-glyoxylate aminotransferase in this disease leads to recurrent nephrolithiasis, nephrocalcinosis, systemic oxalosis, and kidney failure. The aim of this study was to determine the molecular etiology of kidney transplant loss in a young Tunisian individual. We present a young man with end-stage renal disease who received a kidney allograft and experienced early graft failure. There were no improvement in kidney function; he required hemodialysis and graft biopsy revealed calcium oxalate crystals, which raised suspicion of primary hyperoxaluria. Genetic study in the AGXT gene by PCR direct sequencing identified three missense changes in heterozygote state: the p. Gly190Arg mutation next to two other novels not previously described. The classification of the deleterious effect of the missense changes was developed using the summered results of four different mutation assessment algorithms, SIFT, PolyPhen, Mutation Taster, and Align-GVGD. This system classified the changes as polymorphism in one and as mutation in other. The patient was compound heterozygous mutations. Structural analysis showed that the novel mutation, p.Pro28Ser mutation, affects near the dimerization interface of AGT and positioned on binding site instead of the inhibitor, amino-oxyacetic acid (AOA). With the novel AGXT mutation, the mutational spectrum of this gene continues to broaden in our population. The diagnosis of PH1 was not recognized until after renal transplant with fatal consequences, which led us to confirm the importance of screening before planning for kidney transplantation in population with a relatively high frequency of AGXT mutation carriers.
authors: Biochemistry Department, LR12SP11, Sahloul University Hospital, 4054 Sousse, Tunisia. Electronic address: sawsen_mdimegh@live.fr.
authors: Saoussen
authors: S
authors: M'dimegh
authors: Biochemistry Department, LR12SP11, Sahloul University Hospital, 4054 Sousse, Tunisia. Electronic address: asmaomezzine2@gmail.com.
authors: Asma
authors: A
authors: Omezzine
authors: UR06SP20, Laboratory of Microbiology, Sahloul University Hospital, 4054 Sousse, Tunisia. Electronic address: benhamida.meriam@gmail.com.
authors: Mériam Ben
authors: MB
authors: Hamida-Rebai
authors: Laboratory of Inborn Metabolic Diseases, Centre de Biologie Est, Hospices Civils de Lyon, Lyon 69677, Bron Cedex, France. Electronic address: cecile.acquaviva-bourdain@chu-lyon.fr.
authors: Cécile
authors: C
authors: Aquaviva-Bourdain
authors: Biochemistry Department, LR12SP11, Sahloul University Hospital, 4054 Sousse, Tunisia. Electronic address: ibtihelle.hajmbarek@yahoo.fr.
authors: Ibtihel
authors: I
authors: M'barek
authors: Nephrology Department, Sahloul University Hospital, 4054 Sousse, Tunisia. Electronic address: wissal.sah@yahoo.fr.
authors: Wissal
authors: W
authors: Sahtout
authors: Nephrology Department, Sahloul University Hospital, 4054 Sousse, Tunisia. Electronic address: dorsafe.zellama@yahoo.fr.
authors: Dorsaf
authors: D
authors: Zellama
authors: Laboratory of Inborn Metabolic Diseases, Centre de Biologie Est, Hospices Civils de Lyon, Lyon 69677, Bron Cedex, France. Electronic address: genevieve.souche@chu-lyon.fr.
authors: Geneviéve
authors: G
authors: Souche
authors: Nephrology Department, Sahloul University Hospital, 4054 Sousse, Tunisia. Electronic address: abdellatif_achour@rns.tn.
authors: Abdellatif
authors: A
authors: Achour
authors: Pediatric Department, LR12SP11, Sahloul University Hospital, 4054 Sousse, Tunisia. Electronic address: abroug.saoussen@rns.tn.
authors: Saoussen
authors: S
authors: Abroug
authors: Biochemistry Department, LR12SP11, Sahloul University Hospital, 4054 Sousse, Tunisia. Electronic address: ali.bouslama@rns.tn.
authors: Ali
authors: A
authors: Bouslama
mesh_terms: D000328:Adult; D002129:Calcium Oxalate / Q000378:metabolism; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005820:Genetic Testing; D005838:Genotype; D006038:Glyoxylates / Q000378:metabolism; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000235:genetics*; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000628:therapy*; D016030:Kidney Transplantation; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D000637:Transaminases / Q000235:genetics*; D014416:Tunisia; D055815:Young Adult
chemical_list: D006038:Glyoxylates; D002129:Calcium Oxalate; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase; C031150:glyoxylic acid
keywords: AGXT; Primary hyperoxaluria type 1; Renal failure; Renal transplantation