Characteristics of the genotype and phenotype in Chinese primary hyperoxaluria type 1 populations

Zhao, Fei; Li, Jun; Tang, Lei; Li, Chunming; Wang, Wenying; Chen, Ning

doi:10.1007/s00240-020-01201-x

Cited by 9 publications

(13 citation statements)

References 27 publications

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“…In our study, pt7 was homozygous for the variant c.823_824dup and lived with stable disease. This differed from previously reported conclusions, which suggested that this variant site was associated with a poorer prognosis ( Zhao et al, 2021 ). So far, the variant c.33dup (p. K12Qfs) was documented as the second most common AGXT variant in the Chinese population ( van Woerden et al, 2003 ; Monico et al, 2007 ; He et al, 2019 ; Zhao et al, 2021 ).…”

Section: Discussioncontrasting

confidence: 99%

“…This differed from previously reported conclusions, which suggested that this variant site was associated with a poorer prognosis ( Zhao et al, 2021 ). So far, the variant c.33dup (p. K12Qfs) was documented as the second most common AGXT variant in the Chinese population ( van Woerden et al, 2003 ; Monico et al, 2007 ; He et al, 2019 ; Zhao et al, 2021 ). Variant c.679-680 + 2del has been reported to have apparent ethnic associations with Chinese PH1 patients ( Coulter-Mackie and Rumsby, 2004 ; Coulter-Mackie et al, 2008 ).…”

Section: Discussioncontrasting

confidence: 99%

“…In the previous studies, the most frequent PH1 variants in the Chinese population were c.823_824dup, c.33dup and c.679-680 + 2del ( Coulter-Mackie and Rumsby, 2004 ; Coulter-Mackie et al, 2008 ; Du et al, 2018 ; Li et al, 2018 ; He et al, 2019 ; Lin et al, 2021 ; Zhao et al, 2021 ). In our study, pt7 was homozygous for the variant c.823_824dup and lived with stable disease.…”

Section: Discussionmentioning

confidence: 88%

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Four novel variants identified in primary hyperoxaluria and genotypic and phenotypic analysis in 21 Chinese patients

et al. 2023

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Background: Primary hyperoxaluria (PH) is a rare genetic disorder characterized by excessive accumulation of oxalate in plasma and urine, resulting in various phenotypes due to allelic and clinical heterogeneity. This study aimed to analyze the genotype of 21 Chinese patients with primary hyperoxaluria (PH) and explore their correlations between genotype and phenotype.Methods: Combined with clinical phenotypic and genetic analysis, we identified 21 PH patients from highly suspected Chinese patients. The clinical, biochemical, and genetic data of the 21 patients were subsequently reviewed.Results: We reported 21 cases of PH in China, including 12 cases of PH1, 3 cases of PH2 and 6 cases of PH3, and identified 2 novel variants (c.632T > G and c.823_824del) in AGXT gene and 2 novel variants (c.258_272del and c.866-34_866-8del) in GRHPR gene, respectively. A possible PH3 hotspot variant c.769T > G was identified for the first time. In addition, patients with PH1 showed higher levels of creatinine and lower eGFR than those with PH2 and PH3. In PH1, patients with severe variants in both alleles had significantly higher creatinine and lower eGFR than other patients. Delayed diagnosis still existed in some late-onset patients. Of all cases, 6 had reached to end-stage kidney disease (ESKD) at diagnosis with systemic oxalosis. Five patients were on dialysis and three had undergone kidney or liver transplants. Notably, four patients showed a favorable therapeutic response to vitamin B6, and c.823_824dup and c.145A > C may be identified as potentially vitamin B6-sensitive genotypes.Conclusion: In brief, our study identified 4 novel variants and extended the variant spectrum of PH in the Chinese population. The clinical phenotype was characterized by large heterogeneity, which may be determined by genotype and a variety of other factors. We first reported two variants that may be sensitive to vitamin B6 therapy in Chinese population, providing valuable references for clinical treatment. In addition, early screening and prognosis of PH should be given more attention. We propose to establish a large-scale registration system for rare genetic diseases in China and call for more attention on rare kidney genetic diseases.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 88%

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Four novel variants identified in primary hyperoxaluria and genotypic and phenotypic analysis in 21 Chinese patients

et al. 2023

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“…1a). Although more than 200 mutations have been described in AGXT, p.Gly170Arg is the most frequent in Western populations and accounts for approximately 28-30% of mutant alleles [8][9][10] ; c.33dupC is more common in other regions 8,9,11,12 .…”

Section: Rationale For Genetic Assessment In Phmentioning

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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“…Two other variants, c.33dupC and p.I244T, account for 12–15% [ 2 , 20 ] and 6% [ 20 ] respectively, although the latter occurs more frequently in populations of Spanish and North African descent with frequencies as high as 84% in unrelated Moroccans [ 2 , 24 ] and 92% in the Canaries [ 25 ]. Other ethnic groups may show a completely different spectrum of mutations: For example, the p.G170R variant is rare in individuals of Pakistani descent in whom p.G350D is more common and is notably absent in the Chinese population in which c.33-dupC is more prominent with little overlap with the Caucasian pattern of mutations [ 2 , 26 – 28 ].…”

Section: Most Common Mutations In Ph Typementioning

confidence: 99%

Genetic assessment in primary hyperoxaluria: why it matters

Mandrile

Beck²,

Acquaviva³

et al. 2022

Pediatr Nephrol

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Accurate diagnosis of primary hyperoxaluria (PH) has important therapeutic consequences. Since biochemical assessment can be unreliable, genetic testing is a crucial diagnostic tool for patients with PH to define the disease type. Patients with PH type 1 (PH1) have a worse prognosis than those with other PH types, despite the same extent of oxalate excretion. The relation between genotype and clinical phenotype in PH1 is extremely heterogeneous with respect to age of first symptoms and development of kidney failure. Some mutations are significantly linked to pyridoxine-sensitivity in PH1, such as homozygosity for p.G170R and p.F152I combined with a common polymorphism. Although patients with these mutations display on average better outcomes, they may also present with CKD stage 5 in infancy. In vitro studies suggest pyridoxine-sensitivity for some other mutations, but confirmatory clinical data are lacking (p.G47R, p.G161R, p.I56N/major allele) or scarce (p.I244T). These studies also suggest that other vitamin B6 derivatives than pyridoxine may be more effective and should be a focus for clinical testing. PH patients displaying the same mutation, even within one family, may have completely different clinical outcomes. This discordance may be caused by environmental or genetic factors that are unrelated to the effect of the causative mutation(s). No relation between genotype and clinical or biochemical phenotypes have been found so far in PH types 2 and 3. This manuscript reviews the current knowledge on the genetic background of the three types of primary hyperoxaluria and its impact on clinical management, including prenatal diagnosis.

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Characteristics of the genotype and phenotype in Chinese primary hyperoxaluria type 1 populations

Cited by 9 publications

References 27 publications

Four novel variants identified in primary hyperoxaluria and genotypic and phenotypic analysis in 21 Chinese patients

Four novel variants identified in primary hyperoxaluria and genotypic and phenotypic analysis in 21 Chinese patients

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

Genetic assessment in primary hyperoxaluria: why it matters

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