Edition of 24 December 2020

A new study published in the American Journal of Medical Genetics identified a family in which individuals were affected with gout, hyperuricemia associated with reduced fractional excretion of uric acid, chronic kidney disease (CKD) and secondary hyperparathyroidism, that are consistent with familial juvenile hyp-eruricemic nephropathy (FJHN). However, single gene testing had not detected mutations in the uromodulin (UMOD) or renin (REN) genes, which cause approximately 30–90% of FJHN. Whole genome sequencing was therefore undertaken, and this identified a heterozygous missense variant in the paired box gene 2 (PAX2) gene, which cosegregated with renal tubulopathy in the family. PAX2 mutations are associated with renal coloboma syndrome (RCS), which is characterized by abnormalities in renal structure and function, and anomalies of the optic nerve. Ophthalmological examination in two adult brothers affected with hyperuricemia, gout, and CKD revealed the presence of optic disc pits, consistent with optic nerve coloboma. This study allowed to revise the diagnosis from FJHN to RCS and highlight the utility of whole genome sequencing analysis.