Clinical utility of genetic testing in Indian children with kidney diseases

Background Kidney diseases with genetic etiology in children present with an overlapping spectrum of manifestations. We aimed to analyze the clinical utility of genetic testing in the diagnosis and management of suspected genetic kidney diseases in children. Methods In this retrospective study, children ≤ 18 years in whom a genetic test was ordered were included. Clinical indications for genetic testing were categorized as Glomerular diseases, nephrolithiasis and/or nephrocalcinoses, tubulopathies, cystic kidney diseases, congenital abnormality of kidney and urinary tract, chronic kidney disease of unknown aetiology and others. Clinical exome sequencing was the test of choice. Other genetic tests ordered were sanger sequencing, gene panel, multiplex ligation-dependent probe amplification and karyotyping. The pathogenicity of the genetic variant was interpreted as per the American College of Medical Genetics classification. Results A total of 86 samples were sent for genetic testing from 76 index children, 8 parents and 2 fetuses. A total of 74 variants were reported in 47 genes. Out of 74 variants, 42 were missense, 9 nonsense, 12 frameshifts, 1 indel, 5 affected the splicing regions and 5 were copy number variants. Thirty-two were homozygous, 36 heterozygous and 6 were hemizygous variants. Twenty-four children (31.6%) had pathogenic and 11 (14.5%) had likely pathogenic variants. Twenty-four children (31.6%) had variants of uncertain significance. No variants were reported in 17 children (22.3%). A genetic diagnosis was made in 35 children with an overall yield of 46%. The diagnostic yield was 29.4% for glomerular diseases, 53.8% for tubular disorders, 81% for nephrolithiasis and/or nephrocalcinoses, 60% for cystic kidney diseases and 50% for chronic kidney disease of unknown etiology. Genetic testing made a new diagnosis or changed the diagnosis in 15 children (19.7%). Conclusion Nearly half (46%) of the children tested for a genetic disease had a genetic diagnosis. Genetic testing confirmed the clinical diagnoses, changed the clinical diagnoses or made a new diagnosis which helped in personalized management.