<i>UMOD</i> Mutations in Chronic Kidney Disease in Taiwan
Huan-Da Chen,
Chih-Chuan Yu,
I-Hsiao Yang,
Chi-Chih Hung,
Mei-Chuan Kuo,
Der-Cherng Tarng,
Jer-Ming Chang,
Daw-Yang Hwang
Affiliations
Huan-Da Chen
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
Chih-Chuan Yu
National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan
I-Hsiao Yang
Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
Chi-Chih Hung
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
Mei-Chuan Kuo
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
Der-Cherng Tarng
Institutes of Physiology and Clinical Medicine, Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming Chiao-Tung University, Taipei 112201, Taiwan
Jer-Ming Chang
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, Taiwan
Daw-Yang Hwang
National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan
UMOD is the first identified and the most commonly mutated gene that causes autosomal dominant tubulointerstitial kidney disease (ADTKD). Recent studies have shown that ADTKD-UMOD is a relatively common cause of chronic kidney disease (CKD). However, the status of ADTKD-UMOD in Taiwan remains unknown. In this study, we identified three heterozygous UMOD 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-UMOD contributed to a small but significant cause of CKD in the Taiwanese population.
