The Genetic and Cellular Basis of Autosomal Dominant Polycystic Kidney Disease-A Primer for Clinicians.

Adrián Cordido,Lara Besada-Cerecedo,Miguel A García-González

doi:10.3389/fped.2017.00279

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic disorders worldwide. In recent decades, the field has undergone a revolution, starting with the identification of causal ADPKD genes, including PKD1, PKD2, and the recently identified GANAB. In addition, advances defining the genetic mechanisms, protein localization and function, and the identification of numerous pathways involved in the disease process, have contributed to a better understanding of this illness. Together, this has led to a better prognosis, diagnosis, and treatment in clinical practice. In this mini review, we summarize and discuss new insights about the molecular mechanisms underlying ADPKD, including its genetics, protein function, and cellular pathways.

Highlights

Polycystic kidney disease (PKD) is a heterogeneous group of monogenic disorders characterized by the bilateral formation and progressive expansion of renal cyst that lead to end stage renal disease (ESRD) [1]
Several studies support this: [1] García-González and colleagues reported genetic interaction between autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) genes in a common pathway [17], [2] it has been reported that autosomal dominant polycystic liver disease (ADPLD) genes (Prkcsh and Sec63), ARPKD gene (Pkhd1) and ADPKD gene (Pkd1) interact with each other suggesting a central role of PC1 in cystogenesis [65], and [3] a developmental window for cystogenesis has been identified, suggesting that timing of secondary events may influence the severity of ADPKD [66]
Cai and colleagues described the effect of several mutations in Pkd1 and Pkd2 in the importance of PCs trafficking to cilia using in vitro and in vivo models, concluding that altered trafficking and dysfunctional maturation of PC complex underlie PKD pathology [71] These facts suggest a central role for PC1 in the cystogenesis process and in regulating the severity of ADPKD, ARPKD, and ADPLD [72]

Summary

Introduction

Polycystic kidney disease (PKD) is a heterogeneous group of monogenic disorders characterized by the bilateral formation and progressive expansion of renal cyst that lead to end stage renal disease (ESRD) [1]. Autosomal dominant polycystic kidney disease is genetically heterogeneous and associated with mutations in PKD1 (responsible of ADPKD-Type I), PKD2 (-Type II), and GANAB.

Results

Conclusion