<i>UMOD</i> Mutations in Chronic Kidney Disease in Taiwan
<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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/9/2265 |
| _version_ | 1797490840055054336 |
|---|---|
| author | Huan-Da Chen Chih-Chuan Yu I-Hsiao Yang Chi-Chih Hung Mei-Chuan Kuo Der-Cherng Tarng Jer-Ming Chang Daw-Yang Hwang |
| author_facet | Huan-Da Chen Chih-Chuan Yu I-Hsiao Yang Chi-Chih Hung Mei-Chuan Kuo Der-Cherng Tarng Jer-Ming Chang Daw-Yang Hwang |
| author_sort | Huan-Da Chen |
| collection | DOAJ |
| description | <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. |
| first_indexed | 2024-03-10T00:38:49Z |
| format | Article |
| id | doaj.art-eebf361c6cb2467ba44b8c9acf50628d |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:38:49Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-eebf361c6cb2467ba44b8c9acf50628d2023-11-23T15:11:55ZengMDPI AGBiomedicines2227-90592022-09-01109226510.3390/biomedicines10092265<i>UMOD</i> Mutations in Chronic Kidney Disease in TaiwanHuan-Da Chen0Chih-Chuan Yu1I-Hsiao Yang2Chi-Chih Hung3Mei-Chuan Kuo4Der-Cherng Tarng5Jer-Ming Chang6Daw-Yang Hwang7Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan 70456, TaiwanDepartment of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, TaiwanDivision of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, TaiwanDivision of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, TaiwanInstitutes of Physiology and Clinical Medicine, Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming Chiao-Tung University, Taipei 112201, TaiwanDivision of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807377, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan<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.https://www.mdpi.com/2227-9059/10/9/2265uromodulinchronic kidney disease (CKD)autosomal dominant tubulointerstitial kidney disease (ADTKD)kidney failure (KF) |
| spellingShingle | Huan-Da Chen Chih-Chuan Yu I-Hsiao Yang Chi-Chih Hung Mei-Chuan Kuo Der-Cherng Tarng Jer-Ming Chang Daw-Yang Hwang <i>UMOD</i> Mutations in Chronic Kidney Disease in Taiwan Biomedicines uromodulin chronic kidney disease (CKD) autosomal dominant tubulointerstitial kidney disease (ADTKD) kidney failure (KF) |
| title | <i>UMOD</i> Mutations in Chronic Kidney Disease in Taiwan |
| title_full | <i>UMOD</i> Mutations in Chronic Kidney Disease in Taiwan |
| title_fullStr | <i>UMOD</i> Mutations in Chronic Kidney Disease in Taiwan |
| title_full_unstemmed | <i>UMOD</i> Mutations in Chronic Kidney Disease in Taiwan |
| title_short | <i>UMOD</i> Mutations in Chronic Kidney Disease in Taiwan |
| title_sort | i umod i mutations in chronic kidney disease in taiwan |
| topic | uromodulin chronic kidney disease (CKD) autosomal dominant tubulointerstitial kidney disease (ADTKD) kidney failure (KF) |
| url | https://www.mdpi.com/2227-9059/10/9/2265 |
| work_keys_str_mv | AT huandachen iumodimutationsinchronickidneydiseaseintaiwan AT chihchuanyu iumodimutationsinchronickidneydiseaseintaiwan AT ihsiaoyang iumodimutationsinchronickidneydiseaseintaiwan AT chichihhung iumodimutationsinchronickidneydiseaseintaiwan AT meichuankuo iumodimutationsinchronickidneydiseaseintaiwan AT dercherngtarng iumodimutationsinchronickidneydiseaseintaiwan AT jermingchang iumodimutationsinchronickidneydiseaseintaiwan AT dawyanghwang iumodimutationsinchronickidneydiseaseintaiwan |