Identification of compound heterozygous patients with primary hyperoxaluria type 1: clinical evaluations and in silico investigations

BMC Nephrology

Research Article

Fatma Makni¹  Amina Lahiani¹  Faiza Fakhfakh²  Houda Kanoun³  Jamil Hachicha⁴  Hichem Mahfoudh⁴  Faiçal Jarraya⁴  Bayen Maalej⁵ 

[1] Laboratoire de Biochimie, Hôpital Habib Bourguiba Sfax, Sfax, Tunisia;Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Sfax, Tunisie;Département des Sciences de la vie, Faculté des Sciences de Sfax, Université des Sfax, Sfax, Tunisia;Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Sfax, Tunisie;Unité de Recherche Pathologie rénale UR12ES14 et Service de Néphrologie, Hôpital Hédi Chaker Sfax, Sfax, Tunisia;Unité de Recherche Pathologie rénale UR12ES14 et Service de Néphrologie, Hôpital Hédi Chaker Sfax, Sfax, Tunisia;Unité de Recherche Pathologie rénale UR12ES14 et Service de Néphrologie, Hôpital Hédi Chaker Sfax, Sfax, Tunisia;Service de Pédiatrie, Hôpital Hédi Chaker Sfax, Sfax, Tunisia;

关键词: Primary hyperoxaluria type 1;    AGT;    AGXT;    Mutation;    Compound heterozygous;   

DOI  :  10.1186/s12882-017-0719-y

 received in 2016-05-05, accepted in 2017-09-20,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundPrimary hyperoxaluria type 1 (PH1) is an autosomal recessive inherited disorder of glyoxylate metabolism in which excessive oxalates are formed by the liver and excreted by the kidneys. Calcium oxalate crystallizes in the urine, leading to urolithiasis, nephrocalcinosis, and consequent renal failure if treatment is not initiated promptly. Mutations in the AGXT gene which encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase are responsible of PH1. In the present work, we aimed to analyze AGXT gene and in silico investigations performed in four patients with PH1 among two non consanguineous families.MethodsExhaustive gene sequencing was performed after PCR amplification of coding exons and introns boundaries. Bioinformatic tools were used to predict the impact of AGXT variants on gene expression as well as on the protein structure and function.ResultsDirect sequencing of all exons of AGXT gene revealed the emergence of multiple mutations in compound heterozygous state in the two studied families. Two patients were compound heterozygous for the c.731 T > C, c.32C > T, c.1020A > G and c.33_34insC and presented clinically with recurrent urinary tract infection, multiple urolithiasis and nephrocalcinosis under the age of 1 year and a persistent hyperoxaluria at the age of diagnosis. The two other patients presenting a less severe phenotypes were heterozygous for c.731 T > C and homozygous for the c.32C > T and c.1020A > G or compound heterozygous for c.26C > A and c.65A > G variants.ConclusionIn Summary, we provided relevance regarding the compound heterozygous mutations in non consanguineous PH1 families with variable severity.

【 授权许可】

CC BY   
© The Author(s). 2017