Polycystic kidney disease (PKD) and Alport syndrome (AS) are serious inherited disorders associated with renal disease, and thalassemia is a hereditary blood disease with a high prevalence in south China. Here, we report an exceptional PKD coincidence of thalassemia minor and AS (diagnosed genetically) in a large Chinese family. Whole genome next-generation sequencing (NGS) was performed on the proband, and all family members underwent clinical evaluation. Sanger sequencing was used to validate the mutations distinguished by NGS. The pathogenic potential of the variants were evaluated by Polymorphism Phenotyping v2 (PolyPhen-2), Sorting Intolerant From Tolerant (SIFT) algorithm, and MutationTaster. Immunohistochemical, Western blot, immunofluorescent, and TdT-mediated dUTP nick-end labeling (TUNEL) analyses were performed to investigate polycystin 1 (PC1) expression, and cell proliferation and apoptosis in kidney tissues from the proband and normal control. A novel frameshift polycystic kidney disease 1 (PKD1) mutation (c.3903delC, p.A1302Pfs) was identified to be responsible for renal disease in this family. PC1 expression, and cell proliferation and apoptosis were significantly increased in the kidney tissues of the proband. Moreover, a deletion of approximately 19.3 kb of DNA with α-globin genes (_ _SEA) was associated with thalassemia minor in the family. In addition, a collagen type IV α 5 chain (COL4A5) variant (c.2858G>T, rs78972735), annotated as a pathogenic mutation in dbSNP and human gene mutation database (HGMD), was found in four family members with no clinical traits of AS. A novel pathogenic PKD1 mutation (c.3903delC) and (_ _SEA) thalassemia deletion were found to be responsible for the clinical symptoms in this family. The reported pathogenic COL4a5 variant (c.2858G>T, rs78972735) was not pathogenic alone.
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October 2017
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In this issue of Clinical Science, Thompson et al (pages 2489-2501) describe their research on the capacity of protein tyrosine phosphatase 1B inhibitor to reverse atherosclerotic plaque formation in a mouse model. The cover image shows aortic root sections of mice fed on a high-fat-diet that are stained with Oil Red - a method the authors used to quantify plaque formation in this study.
Research Article|
September 22 2017
Genetic diagnosis of polycystic kidney disease, Alport syndrome, and thalassemia minor in a large Chinese family
Yun Miao;
Yun Miao
*
1Organ Transplant Department, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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Jun Xiong;
Jun Xiong
*
2Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
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Xuelian Zhang;
Xuelian Zhang
2Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
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Huajie Huang;
Huajie Huang
2Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
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Lixin Yu;
Lixin Yu
1Organ Transplant Department, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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Jianfan Chen;
Jianfan Chen
2Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
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Wenfeng Deng;
Wenfeng Deng
1Organ Transplant Department, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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Huiling Xu;
Huiling Xu
2Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
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Rumin Liu;
Rumin Liu
1Organ Transplant Department, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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Chenglin Xiang;
Chenglin Xiang
3Central Laboratory, Southern Medical University, Guangzhou 510515, China
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Xiangmin Xu;
Xiangmin Xu
2Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
4Guangdong Key Laboratory of Biological Chip, Southern Medical University, Guangzhou 510515, China
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Fu Xiong
2Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
4Guangdong Key Laboratory of Biological Chip, Southern Medical University, Guangzhou 510515, China
Correspondence: Fu Xiong (xiongfu@smu.edu.cn)
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Publisher: Portland Press Ltd
Received:
April 09 2017
Revision Received:
July 31 2017
Accepted:
August 16 2017
Accepted Manuscript online:
August 21 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (19): 2427–2438.
Article history
Received:
April 09 2017
Revision Received:
July 31 2017
Accepted:
August 16 2017
Accepted Manuscript online:
August 21 2017
Citation
Yun Miao, Jun Xiong, Xuelian Zhang, Huajie Huang, Lixin Yu, Jianfan Chen, Wenfeng Deng, Huiling Xu, Rumin Liu, Chenglin Xiang, Xiangmin Xu, Fu Xiong; Genetic diagnosis of polycystic kidney disease, Alport syndrome, and thalassemia minor in a large Chinese family. Clin Sci (Lond) 1 October 2017; 131 (19): 2427–2438. doi: https://doi.org/10.1042/CS20170245
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