Genetic Testing in Pediatric Kidney Disease
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Genetic Testing in Pediatric Kidney Disease Veronica Arora 1 & Kanav Anand 2 & Ishwar Chander Verma 1 Received: 9 December 2019 / Accepted: 13 January 2020 # Dr. K C Chaudhuri Foundation 2020
Abstract The advent of next gene sequencing technology has led to the publication of a profusion of papers on monogenic contributions to pediatric kidney disorders. It started with the discovery of mutations in the podocin gene in steroid resistant nephrotic syndrome (SRNS). It is realized now that genetic disorders contribute to about 30% of chronic renal diseases in children, and significantly to many other kidney disorders. This paper covers briefly the new genetic technologies, the benefits of genetic testing, and the indication for genetic testing in various kidney disorders. It covers SRNS, congenital anomalies of the kidney, cystic kidney disease, tubulopathies, nephronophthisis, Fabry disease, Alport and Lowe syndrome. Atypical hemolytic uremic syndrome, renal tubular acidosis and nephrolithiasis are also covered briefly. It is hoped that this paper will encourage the pediatricians to investigate monogenic disorders of the kidney as it helps in their proper classification, informs prognosis, suggests specific treatment and aids in genetic and reproductive counseling. Keywords Genetic testing . Genetic disorders . Pediatric kidney disease . SRNS . CAKUT . Tubulopathies . Atypical hemolytic uremic syndrome . RTA . Alport syndrome . Next gene sequencing
Introduction SK, a 3-y-old boy had an attack of nephrotic syndrome. He was initiated on steroid therapy. At the end of 4 wk there was very little clinical response and he was classified as steroid resistant. A gene test was ordered, and a homozygous pathogenic variant was detected (Arg367Cys) in NPHS1 (podocin) gene. Just imagine that the change in one DNA base of C > T in the 3.3 billion bases in this individual was the root cause of this problem. In fact, the discovery of variants in podocin gene led to the understanding of the role of podocytes in glomerular filtration. Gradually the importance of monogenic disorders in kidney disease was realized. Almost 35% of early onset
* Ishwar Chander Verma [email protected] 1
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India
2
Division of Pediatric Nephrology and Renal Transplantation, Institute of Child Health, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India
chronic kidney diseases (EOCKD) are due to single gene disorders.
Benefits of Genetic Testing Genetic testing cuts short the diagnostic odyssey of patients looking for a diagnosis for their problems and enables a precise diagnosis. It avoids a kidney biopsy, which is always a painful experience. Identifying a specific gene informs the pathway involved and throws light on the pathogenesis. This can facilitate targeted therapy. Through genotype-phenotype correlation it also provides prognosis of the disorder, often better than a kidney biopsy. Occasionally, it may reveal a disorder amenable to
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