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

Murad, Hossam; Alhalabi, Mohamad Baseel; Dabboul, Amir; Alfakseh, Nour; Nweder, Mohamad Sayah; Zghib, Youssef; Wannous, Hala

doi:10.1186/s12920-021-00996-x

“…While in the Arab population, 70% of PH1 patients have gene variants located in exons 1, 2, 5, 7, and 10. DNA sequencing of the above five exons showed a diagnostic sensitivity of 82.22% [ 43 , 45 – 47 ]. In the Chinese population, gene variants in exons 1, 2, 6, and 8 are the most common, accounting for 78% of all variants.…”

Section: Discussionmentioning

confidence: 99%

“…While in the Arab population, 70% of PH1 patients have gene variants located in exons 1, 2, 5, 7, and 10. DNA sequencing of the above five exons showed a diagnostic sensitivity of 82.22% [43,[45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Case series and literature review of primary hyperoxaluria type 1 in Chinese patients

Wu,

Song,

He

et al. 2023

Urolithiasis

2

0

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Based on the single-center case reports and all reported patients with primary hyperoxaluria type 1 (PH1) in China, this study discussed the clinical and genetic characteristics of this disease retrospectively. We reported and validated a novel genetic variation c.302 T > G: the clinical phenotypes of the two siblings were similar, in which both had onset in infancy, mainly manifested as renal insufficiency, and died within 6 months out of end-stage renal disease. The literature review is the first to summarize the Chinese patients with PH1 up to now. Forty-eight Chinese patients were included, containing 7 adults and 41 children. The median onset age was 51 months, and the ratio of male to female was 2.69:1. It showed a poor prognosis: 51.1% of Chinese primary hyperoxaluria type 1 patients suffered from end-stage renal disease, and 38.9% of patients died. Urolithiasis was the most common clinical manifestation both in adults and children, while infant-onset patients generally presented with renal insufficiency and had a higher mortality of 75.0%. One hundred and forty-nine AGXT mutant alleles are currently known in the Chinese population, c.33dupC and c.815_816insGA were the most common AGXT genes, accounting for 12.0% and 10.1% of allele frequencies, respectively. The exons 1, 2, 6, and 8 were the most common locations of gene variants, accounting for 78% of all variants, which will be promising targets of DNA sequencing for primary hyperoxaluria type 1.

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“…In the present study cohort, both missense and frameshift mutations were common types in AGXT. The three most prevalent variants, c.508G>A, c.33dup, and c.731T>C, are commonly seen in European and North American populations, while c.731T>C and c.33dup are the most common variants in Tunisia and Syria, respectively [7,[21][22][23]. To date, three variants have been identified as possible hotspot mutations in the Chinese population, namely, c.33dup, c.815_816insGA, and c.679_680delAA, and c.815_816insGA is the main variant identified in the Chinese population [6,11].…”

Section: Discussionmentioning

confidence: 99%

Genotype and Phenotype Characteristics of Chinese Pediatric Patients with Primary Hyperoxaluria

Ge,

Liu,

Zhan

et al. 2023

Human Mutation

0

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Primary hyperoxaluria (PH) is a rare monogenic disorder characterized by recurrent kidney stones, nephrocalcinosis, and renal impairment. To study the genotype and phenotype characteristics, we evaluated the clinical data of 42 Chinese pediatric PH patients who were diagnosed from May 2016 to April 2022. We found that patients with the PH3 type showed an earlier age of onset than those with the PH1 and PH2 types (1 versus 5 and 8 years, respectively, P < 0.001 ). Urine citrate was significantly lower in PH1 and PH2 patients than that in PH3 patients (91.81 and 85.56 versus 163.9 μg/mg, respectively, P = 0.044 ). Spot urine oxalate levels were slightly higher in PH1 than that in PH2 and PH3 patients (457.9 versus 182.38 and 309.14 μg/mg, respectively, P = 0.189 ). A significant negative correlation between the urine calcium/creatinine ratio and the oxalate/creatinine ratio was observed in the entire PH cohort ( r = − 0.360 , P = 0.04 ) and the PH3 cohort ( r = − 0.674 , P = 0.003 ). PH-causative genes showed hotspot mutations or regions, including c.815_816insGA and c.33dup in AGXT, 864_865del in GRHPR, and exon 6 skipping and c.769T>G in HOGA1. In the PH1 cohort, the estimated glomerular filtration rate (eGFR) was lowest in patients with heterozygous c.33dup. In the PH3 cohort, patients with heterozygous exon 6 skipping presented the lowest eGFR and a significant decrease in the renal survival advantage. In summary, PH1 patients exhibit much more severe phenotypes than those with other types. Hotspot mutations or regions exist in patients with all types of PH and show differences among ethnicities. Genotype-phenotype correlations are observed in PH1 and PH3.

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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

Groothoff

¹

,

Metry

²

,

Deesker

³

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

Cited by 3 publications

References 30 publications

Case series and literature review of primary hyperoxaluria type 1 in Chinese patients

Case series and literature review of primary hyperoxaluria type 1 in Chinese patients

Genotype and Phenotype Characteristics of Chinese Pediatric Patients with Primary Hyperoxaluria

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

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