Molecular analysis of the AGXT gene in patients suspected with hyperoxaluria type 1 and three novel mutations from Turkey

Isiyel, Emel; Ezgü, Sevcan Azime Bakkaloğlu; Çalışkan, Salim; Akman, Sema; Akil, İpek; Tabel, Yılmaz; Akıncı, Nurver; Özdoğan, Elif Bahat; Özel, Ahmet; Eroğlu, Fehime Kara; Ezgu, Fatih Süheyl

doi:10.1016/j.ymgme.2016.10.011

Cited by 6 publications

(8 citation statements)

References 25 publications

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“…From Table 3, we found that the degree of Coagulation factor II9 (F2) was 27, which ranked first among these 10 genes. Then, the following genes were plasminogen10 (PLG; degree= 21), enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase11 (EHHADH; degree= 20), alanine-glyoxylate and serine–pyruvate aminotransferase12 (AGXT; degree= 15), alpha 2-HS glycoprotein (AHSG; degree= 15),13 carboxypeptidase B214 (CPB2; degree= 14), aldehyde dehydrogenase 8 family member A115 (ALDH8A1; degree= 14), serpin family D member 1 (SERPIND1; degree= 12), serpin family F member 216 (SERPINF2; degree= 11), serine hydroxyl-methyltransferase 117 (SHMT1; degree= 11). All of these hub genes were downregulated in CCA.…”

Section: Resultsmentioning

confidence: 99%

Five Hub Genes Can Be The Potential DNA Methylation Biomarkers For Cholangiocarcinoma Using Bioinformatics Analysis

Chen¹,

Wu²,

He³

et al. 2019

OTT

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BackgroundCholangiocarcinoma (CCA) is a subtype of highly malignant hepatic tumor, which has low 5-year survival rate and poor clinical outcome. Only a few patients can be detected early and accepted with the surgery. Most of CCA patients are diagnosed in advanced stage, and the treatments are limited. As for the inoperable, advanced CCA patients, chemotherapy is the main treatment, due to lacking molecular targets, therapeutic effect is limited.Materials and methodsTo explore potential therapeutic targets for CCA, we analyzed three microarray datasets derived from the Gene Expression Omnibus (GEO) database. Then, we used GEO2R tools of NCBI to discover the differentially expressed genes (DEGs) from the CCA and normal liver tumor microarrays (TMA). Subsequently, we used the Database for Annotation, Visualization and Integrated Discovery (DAVID GO) to perform the Gene Ontology function (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, we carried out the Cytoscape software to search for the hub genes downregulated in CCA and identify the protein–protein interaction (PPI) of these genes. Besides, we used the GEPIA tool to evaluate the differential expressions of hub genes in CCA patients. Then, we also used MEXPRESS database to detect the promoter methylation levels of hub genes in CCA and normal tissue samples. In addition, we evaluated the expression of these genes in CCA lines and normal bile tract cells after 5-AZA (DNA methyltransferase inhibitor) treatment.ResultsA total of 115 downregulated DEGs were identified. Among them, 10 hub genes with a high degree of connectivity were picked out. Among these 10 hub genes, F2, AHSG, ALDH8A1, SERPIND1 and AGXT showed higher DNA methylation levels of promoter in CCA compared with normal liver tissues. Therefore, these 5 genes may be the potential DNA methylation biomarkers and therapeutic targets in CCA.

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Section: Resultsmentioning

confidence: 99%

Five Hub Genes Can Be The Potential DNA Methylation Biomarkers For Cholangiocarcinoma Using Bioinformatics Analysis

Chen¹,

Wu²,

He³

et al. 2019

OTT

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“…In Western Europe and North America it accounts for 1 -2% of the pediatric ESRD population but this may reach >10% in countries where there is a high rate of consanguinity, such as North Africa and Middle East. 2,4 Its highly heterogeneous presentation and unfamiliarity with the disease among physicians (due to its rarity) play a major role in diagnostic delay. A high level of suspicion is necessary for an early diagnosis.…”

Section: Figurementioning

confidence: 99%

“…2 An early and accurate diagnosis and treatment in PH1 are essential for achieving better short -and long -term outcomes. 4…”

Section: Figurementioning

confidence: 99%

Primary hyperoxaluria type 1 – two case reports

Ganhão

Borges

Amorim

et al. 2020

pjnh

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Background: Primary hyperoxaluria type 1 is a rare autosomal recessive inherited disease, caused by mutations in AGXT gene, with an estimated incidence of 1:100.000 live births per year in Europe. Over 50% present with end stage renal disease at diagnosis. Case reports: The first case is a 14-year-old boy, second child to consanguineous parents, with history of recurrent lithiasis and ureteral dilatation starting 5 years before. Urine/stone analysis revealed calcium oxalate monohydrate crystals and markedly elevated urine oxalate excretion. Genetic tests confirmed a mutation in AGXT gene, c.1151T>C, in homozygosity. Two years after, nephrocalcinosis was identified and glomerular filtration rate gradually declined. Oxalate deposition in solid organs was excluded and successful orthotopic liver transplantation was performed, with stabilization of glomerular filtration rate. The second case is a 16-year-old girl, with recurrent episodes of renal colic. At diagnosis, she had obstructive hydronephrosis, multiple kidney stones and an estimated glomerular filtration of 42.1mL/min/1.73m 2. Metabolic study showed hypocitraturia and hyperoxaluria. With dietetic measures and irregular treatment, urine oxalate excretion remained high but renal function improved. Genetic tests confirmed the presence of two pathologic variants in AGXT gene: c.731T>C and c.1151T>C in compound heterozygous. Conclusions: Recurrent urolithiasis and nephrocalcinosis in children along with family history/consanguinity should raise the suspicion of Primary Hyperoxaluria type 1. Conservative treatment may increase renal survival. Effects of systemic oxalosis must be screened when glomerular filtration rate declines below 30-50mL/min/1.73m 2 , and sequential or combined liver and kidney transplantation should be considered.

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“…(Williams et al 2009). The mutation, c.815_816insGA, has been described in different ways of notation, such as c.817insAG (Yuen et al 2004), c.823_824dupAG (Li et al 2014), c.823_824dupGA (Isiyel et al 2016), and c.815_816insGA (Cui et al 2017), although the mutation results in the same frame shit. Such a difference in the notation is probably due to the presence of GA repeats (Fig.…”

Section: Features Of the Identified Mutationsmentioning

confidence: 99%

A Putative Mutation Hotspot of the AGXT Gene Associated with Primary Hyperoxaluria Type 1 in the Chinese Population

Yang

et al. 2018

Tohoku J. Exp. Med.

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Primary hyperoxaluria type 1 (PH1), a rare autosomal recessive disorder, is characterized by renal stones, nephrocalcinosis, and chronic kidney disease. PH1 is caused by defects in alanine glyoxylate aminotransferase (AGT, 392 amino-acid residues), which is encoded by the alanine-glyoxylate and serinepyruvate aminotransferase (AGXT) gene. This study aimed to determine the clinical, biochemical, and mutation spectrum of patients with PH1 from mainland China. Four patients (two adults and two children, age range: 1 to 34 years) from four unrelated families were admitted because of kidney stones. The adult patients had chronic kidney disease, while the pediatric patients retained the normal kidney function. Four mutations of the AGXT gene were detected, including one novel mutation, c.1015delG (p.V339Sfs*2). One adult male with late-onset PH1 is a compound heterozygote of the c.815_816insGA (p.S275Rfs*38) and c.1015delG (p.V339Sfs*2) mutations. These frame-shift mutations could result in the production of truncated AGT proteins. Other patients include an adult female who is heterozygous for c.473C>T (p. S158L) and c.815_816insGA mutations and two boys that are respectively homozygous for the c.815_816insGA mutation and for the c.614C>T (p.S205L) mutation. Thus, the c.815_816insGA mutation accounts for 4/8 alleles in the present study; importantly, the position c.815 represents the 5′-end of the consecutive wild-type sequence of GAGAGAGA. In conclusion, we describe one novel mutation, c.1015delG, and a common mutation, c.815_816insGA, of the AGXT gene among four unrelated families with PH1. Moreover, we suggest that the short repeat of the GA dinucleotide may represent a mutation hotspot in the Chinese population.

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Molecular analysis of the AGXT gene in patients suspected with hyperoxaluria type 1 and three novel mutations from Turkey

Cited by 6 publications

References 25 publications

<p>Five Hub Genes Can Be The Potential DNA Methylation Biomarkers For Cholangiocarcinoma Using Bioinformatics Analysis</p>

<p>Five Hub Genes Can Be The Potential DNA Methylation Biomarkers For Cholangiocarcinoma Using Bioinformatics Analysis</p>

Primary hyperoxaluria type 1 – two case reports

A Putative Mutation Hotspot of the <i>AGXT </i>Gene Associated with Primary Hyperoxaluria Type 1 in the Chinese Population

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