An accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease
Abstract Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist wer...
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Nature Portfolio
2021
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oai:doaj.org-article:c0a686aca11e40219bd3b9d29019fff52021-12-02T14:34:15ZAn accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease10.1038/s41525-021-00219-32056-7944https://doaj.org/article/c0a686aca11e40219bd3b9d29019fff52021-07-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00219-3https://doaj.org/toc/2056-7944Abstract Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist were recruited from 2017 to 2019. Trio-ES was conducted for the families who had multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early onset or extrarenal features. Pathogenic variants were confirmed in 62 from 115 families post sequencing for 421 individuals including 195 health family members as potential living donors. Seventeen distinct genetic disorders were identified confirming the priori diagnosis in 33 (28.7%) families, modified or reclassified the clinical diagnosis in 27 (23.5%) families, and established a diagnosis in two families with ESRD of unknown etiology. In 14.8% of the families, we detected promising variants of uncertain significance in candidate genes associated with renal development or renal disease. Furthermore, we reported the secondary findings of oncogenes in 4.4% of the patients and known single-nucleotide polymorphisms associated with pharmacokinetics in our cohort to predict the drug levels of tacrolimus and mycophenolate. The diagnostic utility of the genetic findings has provided new clinical insight in most families that help with preplanned renal transplantation.Zhigang WangHongen XuTianchao XiangDanhua LiuFei XuLixiang ZhaoYonghua FengLinan XuJialu LiuYe FangHuanfei LiuRuijun LiXinxin HuJingyuan GuanLongshan LiuGuiwen FengQian ShenHong XuDmitrij FrishmanWenxue TangJiancheng GuoJia RaoWenjun ShangNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-9 (2021) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Medicine R Genetics QH426-470 |
| spellingShingle |
Medicine R Genetics QH426-470 Zhigang Wang Hongen Xu Tianchao Xiang Danhua Liu Fei Xu Lixiang Zhao Yonghua Feng Linan Xu Jialu Liu Ye Fang Huanfei Liu Ruijun Li Xinxin Hu Jingyuan Guan Longshan Liu Guiwen Feng Qian Shen Hong Xu Dmitrij Frishman Wenxue Tang Jiancheng Guo Jia Rao Wenjun Shang An accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease |
| description |
Abstract Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist were recruited from 2017 to 2019. Trio-ES was conducted for the families who had multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early onset or extrarenal features. Pathogenic variants were confirmed in 62 from 115 families post sequencing for 421 individuals including 195 health family members as potential living donors. Seventeen distinct genetic disorders were identified confirming the priori diagnosis in 33 (28.7%) families, modified or reclassified the clinical diagnosis in 27 (23.5%) families, and established a diagnosis in two families with ESRD of unknown etiology. In 14.8% of the families, we detected promising variants of uncertain significance in candidate genes associated with renal development or renal disease. Furthermore, we reported the secondary findings of oncogenes in 4.4% of the patients and known single-nucleotide polymorphisms associated with pharmacokinetics in our cohort to predict the drug levels of tacrolimus and mycophenolate. The diagnostic utility of the genetic findings has provided new clinical insight in most families that help with preplanned renal transplantation. |
| format |
article |
| author |
Zhigang Wang Hongen Xu Tianchao Xiang Danhua Liu Fei Xu Lixiang Zhao Yonghua Feng Linan Xu Jialu Liu Ye Fang Huanfei Liu Ruijun Li Xinxin Hu Jingyuan Guan Longshan Liu Guiwen Feng Qian Shen Hong Xu Dmitrij Frishman Wenxue Tang Jiancheng Guo Jia Rao Wenjun Shang |
| author_facet |
Zhigang Wang Hongen Xu Tianchao Xiang Danhua Liu Fei Xu Lixiang Zhao Yonghua Feng Linan Xu Jialu Liu Ye Fang Huanfei Liu Ruijun Li Xinxin Hu Jingyuan Guan Longshan Liu Guiwen Feng Qian Shen Hong Xu Dmitrij Frishman Wenxue Tang Jiancheng Guo Jia Rao Wenjun Shang |
| author_sort |
Zhigang Wang |
| title |
An accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease |
| title_short |
An accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease |
| title_full |
An accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease |
| title_fullStr |
An accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease |
| title_full_unstemmed |
An accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease |
| title_sort |
accessible insight into genetic findings for transplantation recipients with suspected genetic kidney disease |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/c0a686aca11e40219bd3b9d29019fff5 |
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