Introduction: In pediatric kidney patients, where clinical presentation is often not fully developed and renal biopsy too risky or inconclusive, it may be difficult to establish the underlying pathology. In cases such as these, genetic diagnosis may be used to guide the treatment, prognosis and counselling. Given the large number of genes involved in kidney disease, introducing next generation sequencing with extended gene panels as part of the diagnostic algorithm presents a viable solution.
Methods: A cohort of 87 consecutive independent cases (83 children and 4 terminated pregnancies) with renal disease were recruited. Exome sequencing with MiSeq or NovaSeq 6 000 (Illumina) platforms and analysis of extended gene panels was used for genetic testing.
Results: Depending on the presenting pathology, the cases were grouped as patients with glomerular disease, ciliopathies, congenital anomalies, renal electrolyte imbalances and chronic/acute kidney disease. The overall diagnostic yield was app. 42% (37 out of 87) with most disease-causing mutations found in COL4A3, COL4A4, COL4A5 and PKHD1 genes. A change or clarification of preliminary diagnosis, or adjustment of initial treatment plan based on the results from the genetic testing was made for app. one third of the children with meaningful genetic findings (11 out 37).
Discussion: Our results prove the value of targeted exome sequencing as non-invasive, versatile and reliable diagnostic tool for pediatric renal disease patients. Providing genetic diagnosis will help for better understanding of disease etiology and will give basis for optimal clinical management and insightful genetic counseling.
S. Karger AG, Basel.