Mutational Analysis of Agxt in Tunisian Population with Primary Hyperoxaluria Type 1

M'dimegh, Saoussen; Omezzine, Asma; M'barek, Ibtihel; Moussa, Amira; Mabrouk, Sameh; Kaarout, Hayet; Souche, Geneviéve; Chemli, J.; Aloui, S.; Aquaviva-bourdain, Cécile; Achour, A.; Abroug, S.; Bouslama, Ali

doi:10.1111/ahg.12178

Cited by 12 publications

(12 citation statements)

References 44 publications

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“…In contrast to the Arab Maghreb countries, which have the p.I244T mutation (Maghrebian mutation) as the most frequent mutation [12,21], this mutation was detected in our study in only one patient as a heterozygous state combined with the new mutation (c.140G > A) at a frequency (1.1%).…”

Section: Discussioncontrasting

confidence: 91%

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Molecular analysis of the AGXT gene in Syrian patients suspected with primary hyperoxaluria type 1

et al. 2021

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Background Characterization of the molecular basis of primary hyperoxaluria type 1 (PH-1) in Syria has been accomplished through the analysis of 90 unrelated chromosomes from 45 Syrians patients with PH-1 from different regions. Methods Alanine glyoxylate aminotransferase (AGXT) gene mutations have been analyzed by using molecular detection methods based on the direct DNA sequencing for all exons of the AGXT gene. Results Seventeen pathogenic mutations were detected in our patients. Six mutations were novels. The three most frequent mutations were c.33_34insC (p.Lys12fs) in Exon 1, c.584 T < G; p.Met195Arg in exon 5 and c.1007 T > A (p.Val336Asp) in exon 10, with a frequency of 33.3%, 12.2%, and 11.1%, respectively. Conclusion DNA sequencing used in this study can offer a useful method to investigate the mutations in Syrian PH-1 patients, and could offer an accurate tool for prenatal diagnosis and genetic counseling.

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Section: Discussioncontrasting

confidence: 91%

“…This sequence change replaces tryptophan with arginine at codon 108 of the AGXT protein (p.Trp108Arg). This variant is observed in many individuals affected with AGXT-related conditions [17,21]. This variant has been known to affect AGXT protein function [20,22,23].…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis of the AGXT gene in Syrian patients suspected with primary hyperoxaluria type 1

et al. 2021

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“…The genetic landscape of PH1 in LMICs varies according to the geographical region 96,[120][121][122][123][124][125][126] . Diagnosis is challenging, and diverse diagnostic tools are often unavailable 12,96 .…”

Section: Management Of Ph In Low-resource Countriesmentioning

confidence: 99%

Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope

et al. 2023

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Primary hyperoxaluria (PH) is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis and eventually kidney failure; the subsequent storage of oxalate can cause life-threatening systemic disease. Diagnosis of PH is often delayed or missed owing to its rarity, variable clinical expression and other diagnostic challenges. Management of patients with PH and kidney failure is also extremely challenging. However, in the past few years, several new developments, including new outcome data from patients with infantile oxalosis, from transplanted patients with type 1 PH (PH1) and from patients with the rarer PH types 2 and 3, have emerged. In addition, two promising therapies based on RNA interference have been introduced. These developments warrant an update of existing guidelines on PH, based on new evidence and on a broad consensus. In response to this need, a consensus development core group, comprising (paediatric) nephrologists, (paediatric) urologists, biochemists and geneticists from OxalEurope and the European Rare Kidney Disease Reference Network (ERKNet), formulated and graded statements relating to the management of PH on the basis of existing evidence. Consensus was reached following review of the recommendations by representatives of OxalEurope, ESPN, ERKNet and ERA, resulting in 48 practical statements relating to the diagnosis and management of PH, including consideration of conventional therapy (conservative therapy, dialysis and transplantation), new therapies and recommendations for patient follow-up. SectionsUnanswered questions and research agenda Conclusions

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“…To date, only very few supportive measures are available for patients suffering from PH1, which, together with the severity of the disorder, renders disease management very challenging [ 7 ]. Conservative measures are the cornerstone of PH1 management that can prevent further stone formation and renal function loss [ 1 , 2 , 25 ]. These measures should be initiated as soon as the diagnosis is suspected [ 1 , 2 ].…”

Section: Therapeutic Resourcesmentioning

confidence: 99%

Primary hyperoxaluria type 1 in developing countries: novel challenges in a new therapeutic era

Soliman

Mabrouk

2022

Clinical Kidney Journal

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Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism characterized by marked hepatic overproduction of oxalate due to deficiency of hepatic peroxisomal alanine-glyoxylate aminotransferase caused by AGXT gene mutation. One major hallmark of PH1 in developed as well as developing countries (DC) is the diagnostic delay. Notably in DC, where the disease is most prevalent and probably underdiagnosed, there are many challenges in PH1 diagnosis and management, with economic constrains and ethical concerns. This has led to the existing gap in the management of PH1 between developed and DC, which is expected to further deepen with the advent of novel therapeutic agents unless appropriate actions are taken. Until recently, treatment possibilities were limited to supportive measures. Thanks to a better understanding of the molecular basis of the disease a number of new therapies are developed, or being developed, leading to profound changes in management strategies. In this review we discuss the current situation of PH1 in DC as well as the accessibility challenges and the advantages of using promising novel therapeutics to bridge the currently existing gap. We also provide an overview of an integrated approach to ensure equitable access of sustainable therapeutics to PH1 patients in DC. This is expected to reduce global PH1 healthcare disparities, improve its standard of care and reduce disability linked to extrarenal complications of PH1 by implementing personalized medicine.

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Mutational Analysis of Agxt in Tunisian Population with Primary Hyperoxaluria Type 1

Abstract: The two novel mutations detected in our study extend the spectrum of known AGXT gene mutations. The screen for the mutations identified in this study can provide a useful, cost-effective, and first-line investigation in Tunisian PH1 patients.

Cited by 12 publications

References 44 publications

Molecular analysis of the AGXT gene in Syrian patients suspected with primary hyperoxaluria type 1

Molecular analysis of the AGXT gene in Syrian patients suspected with primary hyperoxaluria type 1

Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope

Primary hyperoxaluria type 1 in developing countries: novel challenges in a new therapeutic era

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