scholarly journals A new atypical splice mutation of PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family

2021 ◽  
Author(s):  
J Zhang ◽  
Y Wang ◽  
Y Zhao ◽  
F Liu
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Pathogenic Mutation ◽  
Chinese Family ◽  
Rt Pcr ◽  
Polycystic Kidney ◽  
Renal Disorder ◽  
Truncating Mutation ◽  
Autosomal Dominant Polycystic Kidney

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a very common hereditary renal disorder. Mutations in PKD1 and PKD2, identified as disease-causing genes, cause about 85% and 15% of ADPKD cases, respectively. Methods: In this study, the mutation analysis of PKD genes was implemented in a Chinese family with suspected ADPKD using targeted clinical exome sequencing (CES). The candidate pathogenic variants were further tested by using Sanger sequencing and validated for co-segregation. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to test abnormal splicing and assess its potential pathogenicity. Results: A novel atypical splicing mutation which belongs to unclassified variants (UCVs), IVS6+5G>C, was identified in three family members by CES and was shown to co-segregate only with the affected individuals. RT-PCR reveals the abnormal splicing of exon 6, thus to cause truncating mutation. These findings suggest that the atypical splice site alteration, IVS6+5G>C, in the PKD2 gene is the potential pathogenic mutation leading to ADPKD in the Chinese family. Conclusion: The data available in this study provided strong evidence that IVS6+5G>C is the potential pathogenic mutation for ADPKD. Meantime, this case also emphasizes the significance of functional analysis of UCVs and genotype-phenotype correlation in ADPKD.

scholarly journals A Review of the Imaging Techniques for Measuring Kidney and Cyst Volume in Establishing Autosomal Dominant Polycystic Kidney Disease Progression

2018 ◽  
Vol 48 (1) ◽  
pp. 67-78 ◽  
Author(s):  
Riccardo Magistroni ◽  
Cristiana Corsi ◽  
Teresa Martí ◽  
Roser Torra
Keyword(s):  
Kidney Disease ◽  
Disease Progression ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Imaging Techniques ◽  
Kidney Volume ◽  
Polycystic Kidney ◽  
Renal Disorder ◽  
Renal Imaging ◽  
Autosomal Dominant Polycystic Kidney

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited renal disorder; it is defined by progressive renal cyst formation and subsequent renal enlargement that leads to end-stage renal disease. Until recently, only symptomatic treatments for ADPKD existed. However, therapies that address the underlying pathophysiology of ADPKD are now available and accurate identification of the rate of disease progression is essential. Summary: Published data on the different imaging modalities for measuring kidney and cyst volumes in ADPKD are reviewed. The advantages and drawbacks of the different techniques for calculating kidney volume from renal imaging are also examined, including the use of manual planimetry, stereology, and the ellipsoid equation, as well as the prospect of semi- and fully automatic techniques. The translation of these approaches into clinical practice and their role in informing treatment decisions is discussed. Key Messages: These new therapies require the accurate monitoring of disease progression, which along with diagnosis and prognosis, relies on the effective use of renal imaging techniques. There is growing support for the use of total kidney volume as a measure of cyst burden and as a prognostic predictor of renal function in ADPKD, showing promise as a marker of disease progression.

scholarly journals Autosomal dominant polycystic kidney disease and pioglitazone for its therapy: a comprehensive review with an emphasis on the molecular pathogenesis and pharmacological aspects

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Aryendu Kumar Saini ◽  
Rakesh Saini ◽  
Shubham Singh
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Clinical Manifestations ◽  
Regulatory Body ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Polycystic Kidney ◽  
Renal Disorder ◽  
Autosomal Dominant Polycystic Kidney

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is an inherited chronic kidney disorder (CKD) that is characterized by the development of numerous fluid-filled cysts in kidneys. It is caused either due to the mutations in the PKD1 or PKD2 gene that encodes polycystin-1 and polycystin-2, respectively. This condition progresses into end-stage renal disorder if the renal or extra-renal clinical manifestations remain untreated. Several clinical trials with a variety of drugs have failed, and the only Food and Drugs Administration (FDA) approved drug to treat ADPKD to date is tolvaptan that works by antagonizing the vasopressin-2 receptor (V2R). The pathology of ADPKD is complex and involves the malfunction of different signaling pathways like cAMP, Hedgehog, and MAPK/ERK pathway owing to the mutated product that is polycystin-1 or 2. A measured yet substantial number of preclinical studies have found pioglitazone to decrease the cystic burden and improve the renal function in ADPKD. The peroxisome proliferator-activated receptor-gamma is found on the epithelial cells of renal collecting tubule and when it gets agonized by pioglitazone, confers efficacy in ADPKD treatment through multiple mechanisms. There is only one clinical trial (ongoing) wherein it is being assessed for its benefits and risk in patients with ADPKD, and is expected to get approval from the regulatory body owing to its promising therapeutic effects. This article would encompass the updated information on the epidemiology, pathophysiology of ADPKD, different mechanisms of action of pioglitazone in the treatment of ADPKD with preclinical and clinical shreds of evidence, and related safety updates.

scholarly journals Prediction of Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease Using PKD1/PKD2 Mutations

2020 ◽  
Vol 9 (1) ◽  
pp. 146 ◽  
Author(s):  
Hiroshi Kataoka ◽  
Hinata Fukuoka ◽  
Shiho Makabe ◽  
Rie Yoshida ◽  
Atsuko Teraoka ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Large Deletion ◽  
Polycystic Kidney ◽  
Nonsense Mutations ◽  
Truncating Mutation ◽  
Renal Prognosis ◽  
Autosomal Dominant Polycystic Kidney ◽  
Pkd2 Mutation

Autosomal dominant polycystic kidney disease (ADPKD) patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. However, the differences in disease progression with different mutation types are unclear. Here, a comparative study was conducted on the renal prognosis of patients with ADPKD who were categorized based on genotype (PKD1 versus PKD2 mutation), mutation type (truncating mutation: nonsense, frameshift, splicing mutation, and large deletion; non-truncating mutation: substitution and in-frame deletion), and mutation position. A total of 123 patients visiting our hospital were enrolled. Renal prognosis was poor for those with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations. Despite the truncating mutation, the renal prognosis was relatively favorable for patients with nonsense mutations. Three out of five patients with PKD2 mutation required renal replacement therapy before 58 years of age. In conclusion, we showed that renal prognosis differs according to mutation types in both PKD1 and PKD2, and that it was favorable for those with nonsense mutations among patients with PKD1 truncating mutations. It was also confirmed that renal prognosis was not always favorable in patients with PKD2 mutations. A detailed assessment of mutation types may be useful for predicting the renal prognosis of patients with ADPKD.

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