Abstract
A genetic study is worldwide recommended for children with congenital, infantile, syndromic-form, familial-form, steroid resistance nephrotic syndrome (NS) and suspected hereditary
glomerulopathies. In Thailand, the evaluation of the monogenic cause of NS and hereditary
glomerulopathies 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 and hereditary glomerulopathies nationwide by using more
stringent inclusion criteria than worldwide recommendations. This one-year multicenter study
recruited 20 patients including three congenital NS (CNS), two with infantile NS (INS), 4 with childhood
and 11 suspected hereditary glomerulopathies. We identified causative pathogenic and likely
pathogenic variants in 14 individuals, accounting for 100% of CNS, 50% of INS, 50% of childhood NS,
73% of suspected hereditary glomerulopathies. They carried six genes including NPHS1, LAMB2, CFI,
TRPC6, WT1, and COL4A5. In addition, we identified 5 novel hemizygous COL4A5 gene mutations
responsible for X-linked Alport syndrome. This nationwide study demonstrated that only twenty
patients met the stringent inclusion criteria for WES during one year of the study. The estimated
budget impact was 500,000 per year for WES study of these rare diseases. We provided indications for
WES among children with nephrotic syndrome and suspected hereditary glomerulopathies for the
Thai National Health Security Office for universal healthcare coverage.
