| Summary: | <i>UMOD</i> is the first identified and the most commonly mutated gene that causes autosomal dominant tubulointerstitial kidney disease (ADTKD). Recent studies have shown that ADTKD-<i>UMOD</i> is a relatively common cause of chronic kidney disease (CKD). However, the status of ADTKD-<i>UMOD</i> in Taiwan remains unknown. In this study, we identified three heterozygous <i>UMOD</i> missense variants, c.121T > C (p.Cys41Arg), c.179G > A (p.Gly60Asp), and c.817G > T (p.Val273Phe), in a total of 221 selected CKD families (1.36%). Two of these missense variants, p.Cys41Arg and p.Gly60Asp, have not been reported previously. In vitro studies showed that both uromodulin variants have defects in cell membrane trafficking and excretion to the culture medium. The structure model predicted altered disulfide bond formation in both variants, but only p.Gly60Asp was predicted to cause protein destabilization. Our findings extend the mutation spectrum and indicate that the ADTKD-<i>UMOD</i> contributed to a small but significant cause of CKD in the Taiwanese population.
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