Necesidad de estudio genético para el diagnóstico de algunos casos de acidosis tubular renal distal

Benito, Manuel Heras; García-González, Miguel A.; Recio, María Valdenebro; Ordas, Alvaro Molina; Martínez, Ramiro Callejas; Gómez, María Astrid Rodríguez; García, Lucila; Silva, Lisbeth; Luis, María José Fernández-Reyes

doi:10.1016/j.nefro.2016.06.008

Cited by 5 publications

(2 citation statements)

References 5 publications

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“…In childhood RTA may present as severe disease or go unnoticed, presenting as nephrocalcinosis, chronic kidney disease or stones in adulthood. 10 Patients homozygous for mutations in ATP6V1B1 have dRTA with reduced serum HCO3−. Recessive mutations in ATP6V1B1 and ATP6V0A4 cause deafness.…”

Section: Monogenic Causes Of Stone Diseasementioning

confidence: 99%

“…14 However, recent studies and case reports reveal that genetic testing can uncover complete or incomplete primary dRTA when it remains clinically imperceptible or difficult to diagnose. 6,10 Therapeutic implications for stone patients with dRTA include alkali administration, referral for audiometry testing and monitoring for CKD. 6 Whether diagnosis of idRTA has specific implications has not been established.…”

Section: Monogenic Causes Of Stone Diseasementioning

confidence: 99%

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Personalized Intervention in Monogenic Stone Formers

et al. 2018

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Purpose Treatment of a first-time renal stone consists of acute management followed by medical efforts to prevent stone recurrence. Although nephrolithiasis is roughly 50% heritable, the presence of a family history usually does not affect treatment since most stone disease is regarded as polygenic, ie not attributable to a single gene. Recent evidence has suggested that single mutations could be responsible for a larger proportion of renal stones than previously thought. This intriguing possibility holds the potential to change the management paradigm in stone prevention from metabolically directed therapy to more specific approaches informed by genetic screening and testing. This review synthesizes new findings concerning monogenic kidney stone disease, and provides a concise and clinically useful reference for monogenic causes. It is expected that increased awareness of these etiologies will lead to increased use of genetic testing in recurrent stone formers and further research into the prevalence of monogenic stone disease. Materials and Methods We assembled a complete list of genes known to cause or influence nephrolithiasis based on recent reviews and commentaries. We then comprehensively searched PubMed® and Google Scholar™ for all research on each gene having a pertinent role in nephrolithiasis. We determined which genes could be considered monogenic causes of nephrolithiasis. One gene, ALPL, was excluded since nephrolithiasis is a relatively minor aspect of the disorder associated with the gene (hypophosphatasia). We summarized selected studies and assembled clinically relevant details. Results A total of 27 genes were reviewed in terms of recent findings, mode of inheritance of stone disease, known or supposed prevalence of mutations in the general population of stone patients and specific therapies or considerations. Conclusions There is a distinct opportunity for increased use of genetic testing to improve the lives of pediatric and adult stone patients. Several genes first reported in association with rare disease may be loci for novel mutations, heterozygous disease and forme frustes as causes of stones in the broader population. Cases of idiopathic nephrolithiasis should be considered as potentially having a monogenic basis.

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Section: Monogenic Causes Of Stone Diseasementioning

confidence: 99%

Section: Monogenic Causes Of Stone Diseasementioning

confidence: 99%

Personalized Intervention in Monogenic Stone Formers

et al. 2018

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The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis

Palazzo

Provenzano

Becherucci

et al. 2017

Kidney International

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Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1, ATP6V0A4, and ATP6V1B1 genes have been described as the cause of the disease, transmitted as either an autosomal dominant or recessive trait. Particular clinical features, such as sensorineural hearing loss, have been mainly described in association with mutations in one gene instead of the others. Nevertheless, the diagnosis of distal renal tubular acidosis is essentially based on clinical and laboratory findings, and the series of patients described so far are usually represented by small cohorts. Therefore, a strict genotype-phenotype correlation is still lacking, and questions about whether clinical and laboratory data should direct the genetic analysis remain open. Here, we applied next-generation sequencing in 89 patients with a clinical diagnosis of distal renal tubular acidosis, analyzing the prevalence of genetic defects in SLC4A1, ATP6V0A4, and ATP6V1B1 genes and the clinical phenotype. A genetic cause was determined in 71.9% of cases. In our group of sporadic cases, clinical features, including sensorineural hearing loss, are not specific indicators of the causal underlying gene. Mutations in the ATP6V0A4 gene are quite as frequent as mutations in ATP6V1B1 in patients with recessive disease. Chronic kidney disease was frequent in patients with a long history of the disease. Thus, our results suggest that when distal renal tubular acidosis is suspected, complete genetic testing could be considered, irrespective of the clinical phenotype of the patient

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Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney Diseases

Zhang

Gao

et al. 2021

Kidney Dis

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Background: At least 10% of adults and most of the children who receive renal replacement therapy have inherited kidney diseases. These disorders substantially decrease their life quality and have a large effect on the health-care system. Multisystem complications, with typical challenges for rare disorders, including variable phenotypes and fragmented clinical and biological data, make genetic diagnosis of inherited kidney disorders difficult. In current clinical practice, genetic diagnosis is important for clinical management, estimating disease development, and applying personal treatment for patients. Summary: Inherited kidney diseases comprise hundreds of different disorders. Here, we have summarized various monogenic kidney disorders. These disorders are caused by mutations in genes coding for a wide range of proteins including receptors, channels/transporters, enzymes, transcription factors, and structural components that might also have a role in extrarenal organs (bone, eyes, brain, skin, ear, etc.). With the development of next-generation sequencing technologies, genetic testing and analysis become more accessible, promoting our understanding of the pathophysiologic mechanisms of inherited kidney diseases. However, challenges exist in interpreting the significance of genetic variants and translating them to guide clinical managements. Alport syndrome is chosen as an example to introduce the practical application of genetic testing and diagnosis on inherited kidney diseases, considering its clinical features, genetic backgrounds, and genetic testing for making a genetic diagnosis. Key Messages: Recent advances in genomics have highlighted the complexity of Mendelian disorders, which is due to allelic heterogeneity (distinct mutations in the same gene produce distinct phenotypes), locus heterogeneity (mutations in distinct genes result in similar phenotypes), reduced penetrance, variable expressivity, modifier genes, and/or environmental factors. Implementation of precision medicine in clinical nephrology can improve the clinical diagnostic rate and treatment efficiency of kidney diseases, which requires a good understanding of genetics for nephrologists.

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Necesidad de estudio genético para el diagnóstico de algunos casos de acidosis tubular renal distal

Cited by 5 publications

References 5 publications

Personalized Intervention in Monogenic Stone Formers

Personalized Intervention in Monogenic Stone Formers

The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis

Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney Diseases

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