Abstract
A genetic study is worldwide recommended for children with congenital, infantile, syndromic-form, familial-form, and steroid resistance nephrotic syndrome (NS). In Thailand, the evaluation of the monogenic cause of nephrotic syndrome is limited due to government reimbursement policy. To delineate the disease burden in Thai children and provide data for the government, we employed whole-exome sequencing (WES) to detect monogenic causes of NS nationwide by using more stringent inclusion criteria than worldwide recommendations. This oneyear multicenter study recruited 25 patients including two congenital NS (CNS), one patient with infantile NS (INS), one patient with familial focal segmental glomerulosclerosis, and twenty-one childhood NS with calcineurin resistance NS (CRNS). We identified causative gene mutations in 7 individuals, accounting for 100% of CNS and INS, and 26% of childhood CINS. They carried five previously reported genes including WT1, NPHS1, PLCE1, ACTN4, and COL4A5. In addition, we identified a novel heterozygous G1538+1T SLC6A19 mutation causing hyperglycinuria, nephrolithiasis, and a phenocopy of SRNS. This nationwide study demonstrated that only twentyfive patients met the stringent inclusion criteria for WES during one year of the study. WES allowed for the definite diagnosis and discontinuation of unnecessary immunosuppressive drugs in five patients whose expenses exceeded the WES cost. We provided indications for WES among children with nephrotic syndrome for the Thai National Health Security Office for universal healthcare coverage.
