Whole-Exome Sequencing Application for Genetic Diagnosis of Kidney Diseases: A Study from Southwest of Iran.

Abstract

The kidneys have important and vital functions and provide maintenance of overall body health. Many kidney diseases are caused by single gene defects. Kidney disease is categorized in a heterogeneous group of disorders affecting the kidney, both in structure and function. The end stage of kidney disease is known as kidney failure. Kidney disease is divided into two forms: AKI and CKD (1). Among kidney diseases, polycystic kidney disease (PKD; also known as polycystic kidney syndrome) is revealed to have a genetic background (2). PKD is characterized by the presence of cysts in kidneys. The development and growth of cysts causes abnormalities in the renal tubules. PKD is a clinically and genetically heterogeneous disease (2,3). Clinical characteristics of autosomal dominant and recessive forms of PKD are variable in their penetrance. A range from neonatal death to incidence in old age was reported for PKD (2,4). Disease causing variants in three genes including PKD1 , PKD2, and PKDH1 can cause PKD. The pathogenic variations in the PKD1 and PKD2 genes can cause an autosomal dominant (ADPKD) pattern of inheritance. The pathogenic variations in PKDH1 can cause an autosomal recessive (ARPKD) pattern of inheritance (2). There are more than 500 monogenic causes of CKD (5) and numerous genes are listed in next-generation sequencing (NGS) panels for PKD, including ALG9 , ANKS6 , ATP6V0A4 , BICC1 , GANAB , GLIS3 , HNF1B , INVS , LRP5 , MUC1 , NOTCH2 , NPHP3 , OFD1 , PKD1 , PKD2 , PKHD1 , SEC61A1 , TMEM231 , TSC1 , TSC2 , UMOD , and ZNF423 , etc. (2). For classification, preprognosis, monitoring and treatment, and identification of the etiology of the disease is necessary. It helps us understand the scenario of the disorder’s causes and select the best approach for drug …