Frontiers in Pediatrics (Apr 2021)
Integrating Population Variants and Protein Structural Analysis to Improve Clinical Genetic Diagnosis and Treatment in Nephrogenic Diabetes Insipidus
- 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
Affiliations
- Panli Liao
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Panli Liao
- Tongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, China
- Tianchao Xiang
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Tianchao Xiang
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Tianchao Xiang
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Hongxia Li
- Tongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, China
- Ye Fang
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Ye Fang
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Ye Fang
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Xiaoyan Fang
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Xiaoyan Fang
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Xiaoyan Fang
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Zhiqing Zhang
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Zhiqing Zhang
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Zhiqing Zhang
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Qi Cao
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Qi Cao
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Qi Cao
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Yihui Zhai
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Yihui Zhai
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Yihui Zhai
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Jing Chen
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Jing Chen
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Jing Chen
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Linan Xu
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Linan Xu
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Linan Xu
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Jialu Liu
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Jialu Liu
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Jialu Liu
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Xiaoshan Tang
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Xiaoshan Tang
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Xiaoshan Tang
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Xiaorong Liu
- Department of Nephrology, Beijing Children's Hospital Affiliated to Capital University of Medical Science, Beijing, China
- Xiaowen Wang
- Tongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, China
- Jiangwei Luan
- Tongji Medical College, Wuhan Children's Hospital, Wuhan Maternal and Child Healthcare Hospital, Huazhong University of Science and Technology, Wuhan, China
- Qian Shen
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Qian Shen
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Qian Shen
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Lizhi Chen
- Department of Pediatric, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Xiaoyun Jiang
- Department of Pediatric, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Duan Ma
- Key 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, China
- Hong Xu
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Hong Xu
- Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Fudan University, Shanghai, China
- Hong Xu
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Jia Rao
- Department of Nephrology, National Pediatric Medical Center of China, Children's Hospital of Fudan University, Shanghai, China
- Jia Rao
- Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
- Jia Rao
- State Key Laboratory of Medical Neurobiology, School of Basic Medical Science, Institute of Brain Science, Fudan University, Shanghai, China
- DOI
- https://doi.org/10.3389/fped.2021.566524
- Journal volume & issue
-
Vol. 9
Abstract
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.
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