Integrating Population Variants and Protein Structural Analysis to Improve Clinical Genetic Diagnosis and Treatment in Nephrogenic Diabetes Insipidus
Congenital nephrogenic diabetes insipidus (NDI) is a rare genetic disorder characterized by renal inability to concentrate urine. We utilized a multicenter strategy to investigate the genotype and phenotype in a cohort of Chinese children clinically diagnosed with NDI from 2014 to 2019. Ten boys fro...
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2021.566524/full |
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| author | Panli Liao Panli Liao Tianchao Xiang Tianchao Xiang Tianchao Xiang Hongxia Li Ye Fang Ye Fang Ye Fang Xiaoyan Fang Xiaoyan Fang Xiaoyan Fang Zhiqing Zhang Zhiqing Zhang Zhiqing Zhang Qi Cao Qi Cao Qi Cao Yihui Zhai Yihui Zhai Yihui Zhai Jing Chen Jing Chen Jing Chen Linan Xu Linan Xu Linan Xu Jialu Liu Jialu Liu Jialu Liu Xiaoshan Tang Xiaoshan Tang Xiaoshan Tang Xiaorong Liu Xiaowen Wang Jiangwei Luan Qian Shen Qian Shen Qian Shen Lizhi Chen Xiaoyun Jiang Duan Ma Hong Xu Hong Xu Hong Xu Jia Rao Jia Rao Jia Rao |
| author_facet | Panli Liao Panli Liao Tianchao Xiang Tianchao Xiang Tianchao Xiang Hongxia Li Ye Fang Ye Fang Ye Fang Xiaoyan Fang Xiaoyan Fang Xiaoyan Fang Zhiqing Zhang Zhiqing Zhang Zhiqing Zhang Qi Cao Qi Cao Qi Cao Yihui Zhai Yihui Zhai Yihui Zhai Jing Chen Jing Chen Jing Chen Linan Xu Linan Xu Linan Xu Jialu Liu Jialu Liu Jialu Liu Xiaoshan Tang Xiaoshan Tang Xiaoshan Tang Xiaorong Liu Xiaowen Wang Jiangwei Luan Qian Shen Qian Shen Qian Shen Lizhi Chen Xiaoyun Jiang Duan Ma Hong Xu Hong Xu Hong Xu Jia Rao Jia Rao Jia Rao |
| author_sort | Panli Liao |
| collection | DOAJ |
| description | Congenital nephrogenic diabetes insipidus (NDI) is a rare genetic disorder characterized by renal inability to concentrate urine. We utilized a multicenter strategy to investigate the genotype and phenotype in a cohort of Chinese children clinically diagnosed with NDI from 2014 to 2019. Ten boys from nine families were identified with mutations in AVPR2 or AQP2 along with dehydration, polyuria–polydipsia, and severe hypernatremia. Genetic screening confirmed the diagnosis of seven additional relatives with partial or subclinical NDI. Protein structural analysis revealed a notable clustering of diagnostic mutations in the transmembrane region of AVPR2 and an enrichment of diagnostic mutations in the C-terminal region of AQP2. The pathogenic variants are significantly more likely to be located inside the domain compared with population variants. Through the structural analysis and in silico prediction, the eight mutations identified in this study were presumed to be disease-causing. The most common treatments were thiazide diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). Emergency treatment for hypernatremia dehydration in neonates should not use isotonic saline as a rehydration fluid. Genetic analysis presumably confirmed the diagnosis of NDI in each patient in our study. We outlined methods for the early identification of NDI through phenotype and genotype, and outlined optimized treatment strategies. |
| first_indexed | 2024-12-14T12:21:17Z |
| format | Article |
| id | doaj.art-db563536dcc447d9bfeb59f814196e06 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-12-14T12:21:17Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-db563536dcc447d9bfeb59f814196e062022-12-21T23:01:28ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602021-04-01910.3389/fped.2021.566524566524Integrating Population Variants and Protein Structural Analysis to Improve Clinical Genetic Diagnosis and Treatment in Nephrogenic Diabetes InsipidusPanli Liao0Panli Liao1Tianchao Xiang2Tianchao Xiang3Tianchao Xiang4Hongxia Li5Ye Fang6Ye Fang7Ye Fang8Xiaoyan Fang9Xiaoyan Fang10Xiaoyan Fang11Zhiqing Zhang12Zhiqing Zhang13Zhiqing Zhang14Qi Cao15Qi Cao16Qi Cao17Yihui Zhai18Yihui Zhai19Yihui Zhai20Jing Chen21Jing Chen22Jing Chen23Linan Xu24Linan Xu25Linan Xu26Jialu Liu27Jialu Liu28Jialu Liu29Xiaoshan Tang30Xiaoshan Tang31Xiaoshan Tang32Xiaorong Liu33Xiaowen Wang34Jiangwei Luan35Qian Shen36Qian Shen37Qian Shen38Lizhi Chen39Xiaoyun Jiang40Duan Ma41Hong Xu42Hong Xu43Hong Xu44Jia Rao45Jia Rao46Jia Rao47Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaTongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaTongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, Beijing Children's Hospital Affiliated to Capital University of Medical Science, Beijing, ChinaTongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, ChinaTongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Pediatric, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Pediatric, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institutes of Biomedical Sciences, Fudan University, Shanghai, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaDepartment of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, ChinaShanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, ChinaState Key Laboratory of Medical Neurobiology, School of Basic Medical Science, Institute of Brain Science, Fudan University, Shanghai, ChinaCongenital nephrogenic diabetes insipidus (NDI) is a rare genetic disorder characterized by renal inability to concentrate urine. We utilized a multicenter strategy to investigate the genotype and phenotype in a cohort of Chinese children clinically diagnosed with NDI from 2014 to 2019. Ten boys from nine families were identified with mutations in AVPR2 or AQP2 along with dehydration, polyuria–polydipsia, and severe hypernatremia. Genetic screening confirmed the diagnosis of seven additional relatives with partial or subclinical NDI. Protein structural analysis revealed a notable clustering of diagnostic mutations in the transmembrane region of AVPR2 and an enrichment of diagnostic mutations in the C-terminal region of AQP2. The pathogenic variants are significantly more likely to be located inside the domain compared with population variants. Through the structural analysis and in silico prediction, the eight mutations identified in this study were presumed to be disease-causing. The most common treatments were thiazide diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). Emergency treatment for hypernatremia dehydration in neonates should not use isotonic saline as a rehydration fluid. Genetic analysis presumably confirmed the diagnosis of NDI in each patient in our study. We outlined methods for the early identification of NDI through phenotype and genotype, and outlined optimized treatment strategies.https://www.frontiersin.org/articles/10.3389/fped.2021.566524/fullnephrogenic diabetes insipidusAVPR2AQP2protein structuregenomics |
| spellingShingle | Panli Liao Panli Liao Tianchao Xiang Tianchao Xiang Tianchao Xiang Hongxia Li Ye Fang Ye Fang Ye Fang Xiaoyan Fang Xiaoyan Fang Xiaoyan Fang Zhiqing Zhang Zhiqing Zhang Zhiqing Zhang Qi Cao Qi Cao Qi Cao Yihui Zhai Yihui Zhai Yihui Zhai Jing Chen Jing Chen Jing Chen Linan Xu Linan Xu Linan Xu Jialu Liu Jialu Liu Jialu Liu Xiaoshan Tang Xiaoshan Tang Xiaoshan Tang Xiaorong Liu Xiaowen Wang Jiangwei Luan Qian Shen Qian Shen Qian Shen Lizhi Chen Xiaoyun Jiang Duan Ma Hong Xu Hong Xu Hong Xu Jia Rao Jia Rao Jia Rao Integrating Population Variants and Protein Structural Analysis to Improve Clinical Genetic Diagnosis and Treatment in Nephrogenic Diabetes Insipidus Frontiers in Pediatrics nephrogenic diabetes insipidus AVPR2 AQP2 protein structure genomics |
| title | Integrating Population Variants and Protein Structural Analysis to Improve Clinical Genetic Diagnosis and Treatment in Nephrogenic Diabetes Insipidus |
| title_full | Integrating Population Variants and Protein Structural Analysis to Improve Clinical Genetic Diagnosis and Treatment in Nephrogenic Diabetes Insipidus |
| title_fullStr | Integrating Population Variants and Protein Structural Analysis to Improve Clinical Genetic Diagnosis and Treatment in Nephrogenic Diabetes Insipidus |
| title_full_unstemmed | Integrating Population Variants and Protein Structural Analysis to Improve Clinical Genetic Diagnosis and Treatment in Nephrogenic Diabetes Insipidus |
| title_short | Integrating Population Variants and Protein Structural Analysis to Improve Clinical Genetic Diagnosis and Treatment in Nephrogenic Diabetes Insipidus |
| title_sort | integrating population variants and protein structural analysis to improve clinical genetic diagnosis and treatment in nephrogenic diabetes insipidus |
| topic | nephrogenic diabetes insipidus AVPR2 AQP2 protein structure genomics |
| url | https://www.frontiersin.org/articles/10.3389/fped.2021.566524/full |
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