scholarly journals MO045THE APPLICATION OF A NGS KIDNEY PANEL REVEALED KEY CHALLENGES OF PKD1-2 ANALYSIS: INTERPRETATION OF MISSENSE VARIANTS, SIGNIFICANCE OF VARIANTS IN DUPLICATED REGIONS AND HIGH ALLELIC HETEROGENEITY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Giancarlo Blasio ◽  
Miriam Zacchia ◽  
Francesca Del Vecchio Blanco ◽  
Giovanna Capolongo ◽  
Alessandra Perna ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Rare Variants ◽  
Kidney Diseases ◽  
Great Part ◽  
In Silico Analysis ◽  
Causative Mutation ◽  
Cystic Kidney ◽  
Allelic Heterogeneity ◽  
Missense Variants ◽  
Cystic Kidney Diseases

Abstract Background and Aims Genetic testing has changed the clinical management of inherited kidney diseases patients, improving prognosis, surveillance and therapy. On the other hand, it has put geneticists and clinicians in front of new challenges, as the heterogeneity of these disorders and the high number of variants, with no clear genotype-phenotype correlation. Method 108 patients underwent genetic analysis through a kidney focused NGS panel, named Nephroplex, containing 119 genetic loci associated with inherited kidney disorders. The study aimed to addressed the genetic landscape of cystic individuals and to analyze PKD1 and PKD2 variants in non-cystic individuals. Results Following diagnostic criteria, patients were divided as cystic kidney diseases (n=36) and non-cystic kidney diseases (n=72). Among the group of cystic patients, a causative mutation was detected in 51% of cases. We found thirty-seven PKD1 and PKD2 variants in 26 out of 35 individuals. In particular, 12 variants were shown to be damaging and nine of that were reported in public database, as CLINVAR and Mayo Clinic databases. Among pathogenic variants, twelve were truncating and the remaining were missense variants. Of note, 7 out of 12 damaging PKD1 mutations were located in duplicated regions. Moreover, in three cystic patients, we found a (i) a frameshift hemizygote OFD1 mutation (ii) compound heterozygote PKHD1 variants and (iii) a frameshift MUC1 variant, framing the diagnosis of oro-facio-digital type 1, autosomal recessive polycystic kidney disease and autosomal dominant tubulointerstitial disease, respectively. Interestingly, we detected 28 PKD1-2 rare variants in 21 out of 75 adult non cystic patients (28%). The most were observed in PKD1 genes (82% vs 18% in PKD2). Eighteen of 28 variants were described in the literature as likely benign or as mutations of uncertain significance, while we found 10 novel variants. In silico analysis revealed as pathogenic a frameshift mutation located in exon 15. Of note, the great part of these variations reside into the duplicated PKD1 regions. Conclusion Our data showed that genetic analysis of ADPKD retains unique challenges, given the high degree of homology of PKD1 with his pseudogenes and the high allelic heterogeneity in non-cystic individuals.

Distinct oxylipin alterations in diverse models of cystic kidney diseases

2017 ◽  
Vol 1862 (12) ◽  
pp. 1562-1574 ◽  
Author(s):  
Md Monirujjaman ◽  
Jessay G. Devassy ◽  
Tamio Yamaguchi ◽  
Nikhil Sidhu ◽  
Masanori Kugita ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Cystic Kidney ◽  
Cystic Kidney Diseases

scholarly journals FP068KIDNEY DIFFUSION TENSOR IMAGING (DTI) 3-TESLA :NEW RADIOLOGICAL TECHNIQUE FOR THE STUDY OF HEREDITARY CYSTIC KIDNEY DISEASES

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii87-iii87
Author(s):  
Rosaria Lupica ◽  
Domenico Trimboli ◽  
Valeria Cernaro ◽  
Carmela Aloisi ◽  
Gaetano Montalto ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Diffusion Tensor ◽  
Kidney Diseases ◽  
3 Tesla ◽  
Cystic Kidney ◽  
Cystic Kidney Diseases ◽  
Radiological Technique ◽  
Diffusion Tensor Imaging Dti

scholarly journals Stem cells and fluid flow drive cyst formation in an invertebrate excretory organ

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Hanh Thi-Kim Vu ◽  
Jochen C Rink ◽  
Sean A McKinney ◽  
Melainia McClain ◽  
Naharajan Lakshmanaperumal ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Human Kidney ◽  
Cyst Formation ◽  
Cystic Kidney ◽  
Flow Sensing ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Genetic Interference ◽  
Cystic Kidney Diseases

Cystic kidney diseases (CKDs) affect millions of people worldwide. The defining pathological features are fluid-filled cysts developing from nephric tubules due to defective flow sensing, cell proliferation and differentiation. The underlying molecular mechanisms, however, remain poorly understood, and the derived excretory systems of established invertebrate models (Caenorhabditis elegans and Drosophila melanogaster) are unsuitable to model CKDs. Systematic structure/function comparisons revealed that the combination of ultrafiltration and flow-associated filtrate modification that is central to CKD etiology is remarkably conserved between the planarian excretory system and the vertebrate nephron. Consistently, both RNA-mediated genetic interference (RNAi) of planarian orthologues of human CKD genes and inhibition of tubule flow led to tubular cystogenesis that share many features with vertebrate CKDs, suggesting deep mechanistic conservation. Our results demonstrate a common evolutionary origin of animal excretory systems and establish planarians as a novel and experimentally accessible invertebrate model for the study of human kidney pathologies.

scholarly journals Hypomagnesaemia is absent in children with autosomal dominant polycystic kidney disease

2018 ◽  
Vol 56 (1) ◽  
pp. 90-94 ◽  
Author(s):  
Tomáš Seeman ◽  
Magdaléna Fořtová ◽  
Bruno Sopko ◽  
Richard Průša ◽  
Michael Pohl ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Kidney Diseases ◽  
Differential Diagnostics ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Cystic Kidney Diseases ◽  
Rule Out

Background Hypomagnesaemia is present in 40–50% of children with autosomal dominant renal cysts and diabetes syndrome (RCAD). On the contrary, the prevalence of hypomagnesaemia in children with autosomal dominant polycystic kidney disease (ADPKD) has never been examined. We aimed to investigate whether hypomagnesaemia is present in children with polycystic kidney diseases. Methods Children with cystic kidney diseases were investigated in a cross-sectional study. Serum concentrations of magnesium (S-Mg) and fractional excretion of magnesium (FE-Mg) were tested. Fifty-four children with ADPKD ( n = 26), autosomal recessive polycystic kidney disease (ARPKD) ( n = 16) and RCAD ( n = 12) with median age of 11.2 (0.6–18.6) years were investigated. Results Hypomagnesaemia (S-Mg < 0.7 mmol/L) was detected in none of the children with ADPKD/ARPKD and in eight children (67%) with RCAD. Median S-Mg in children with ADPKD/ARPKD was significantly higher than in children with RCAD (0.89 vs. 0.65 mmol/L, P < 0.01). The FE-Mg was increased in 23% of patients with ADPKD/ARPKD (all had chronic kidney disease stages 2–4) and in 63% of patients with RCAD, where it significantly correlated with estimated glomerular filtration rate (r = −0.87, P < 0.01). Conclusions Hypomagnesaemia is absent in children with ADPKD or ARPKD and could serve as a marker for differential diagnostics between ADPKD, ARPKD and RCAD in children with cystic kidney diseases of unknown origin where molecular genetic testing is lacking. However, while hypomagnesaemia, in the absence of diuretics, appears to rule out ADPKD and ARPKD, normomagnesaemia does not rule out RCAD at least in those aged <3 years.

The patient with haematuria

2015 ◽  
Author(s):  
John Neary ◽  
Neil Turner
Keyword(s):  
Renal Disease ◽  
Acute Inflammation ◽  
Kidney Diseases ◽  
Urinary Tract Obstruction ◽  
Screening Tests ◽  
Cystic Kidney ◽  
Increased Risk ◽  
End Stage ◽  
Cystic Kidney Diseases

Haematuria is a common presenting feature of diseases of the kidney or the renal tract. It is also common in screening tests, single dipstick tests being positive in perhaps 5% of individuals. Age and whether the blood is visible (macroscopic) or non-visible (microscopic) impact largely on whether the explanation is likely to be broadly urological or nephrological. Origins are most commonly simple or urological. Macroscopic bleeding is rare in renal disease, and urine colour is then usually more rather smoky than red except when there is very acute inflammation. The chief urological causes are neoplasia, infection, stones, and trauma. Some traditionally medical conditions may cause simple bleeding; examples include cystic kidney diseases, papillary necrosis and macro- or microvascular ischaemic lesions. The major concern to nephrologists is that even non-visible haematuria may be a pointer to inflammatory or destructive glomerular processes. The presence of casts or dysmorphic red cells is a pointer to glomerular disease; more important in clinical practice are the three other key markers of renal disease: proteinuria, renal impairment in the absence of urinary tract obstruction, and hypertension. In the general population, microscopic haematuria does associate with a long-term increased risk of end-stage renal failure, so after negative investigations, occasional long-term checks are indicated. The case for population screening for haematuria appears weak.

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