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Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP
BACKGROUND: Nephronophthisis-related ciliopathies (NPHP-RC) have strong genotype and phenotype heterogeneity, and the transplantation strategy of Boichis syndrome is still controversial. Our purpose was to examine associations of genotype and phenotype in children with NPHP-RC and analyze the transp...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060285/ https://www.ncbi.nlm.nih.gov/pubmed/36227438 http://dx.doi.org/10.1007/s00467-022-05763-3 |
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author | Li, Jianyi Su, Xiaojun Zhang, Huanxi Wu, Wenrui Li, Jianming Chen, Yanxu Li, Jun Fu, Qian Wu, Chenglin Zhong, Xuhui Wang, Changxi Liu, Longshan |
author_facet | Li, Jianyi Su, Xiaojun Zhang, Huanxi Wu, Wenrui Li, Jianming Chen, Yanxu Li, Jun Fu, Qian Wu, Chenglin Zhong, Xuhui Wang, Changxi Liu, Longshan |
author_sort | Li, Jianyi |
collection | PubMed |
description | BACKGROUND: Nephronophthisis-related ciliopathies (NPHP-RC) have strong genotype and phenotype heterogeneity, and the transplantation strategy of Boichis syndrome is still controversial. Our purpose was to examine associations of genotype and phenotype in children with NPHP-RC and analyze the transplantation strategies of different phenotypes. METHODS: The records of children with NPHP treated at our center from 01/2018 to 03/2021 were retrospectively reviewed. Inclusion criteria were a diagnosis of NPHP, received kidney transplantation, and received whole exome sequencing (WES) or nephropathy gene panel testing. RESULTS: Twenty-nine children with NPHP were included. Nine children (31%) had NPHP1 mutations, and all presented with isolated nephropathy. Eighteen of 20 patients with non-NPHP1 mutations had compound heterozygous mutations, and 70% had extrarenal phenotype. Age at disease presentation (11.2 ± 1.94 years) and the development of kidney failure (12.4 ± 2.70 years) were later in children with NPHP1 mutations than those with non-NPHP1 mutations (5.2 ± 2.83 years and 5.7 ± 2.92 years, respectively). Four of six children with NPHP3 mutations were diagnosed with Boichis syndrome due to liver fibrosis. Isolated kidney transplantation resulted in good outcomes for patients with mild or moderate liver fibrosis without portal hypertension, while cholestasis was common postoperatively and could be resolved with ursodeoxycholic acid. CONCLUSIONS: NPHP1 mutations are the most common in children with NPHP, and the phenotype of NPHP1 mutation is significantly different from that of non-NPHP1 mutation. For NPHP patients with mild to moderate liver fibrosis without portal hypertension, timely treatment of cholestasis could prevent the rapid progression of liver function damage after isolated kidney transplantation. GRAPHICAL ABSTRACT: [Figure: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-022-05763-3. |
format | Online Article Text |
id | pubmed-10060285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-100602852023-03-31 Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP Li, Jianyi Su, Xiaojun Zhang, Huanxi Wu, Wenrui Li, Jianming Chen, Yanxu Li, Jun Fu, Qian Wu, Chenglin Zhong, Xuhui Wang, Changxi Liu, Longshan Pediatr Nephrol Original Article BACKGROUND: Nephronophthisis-related ciliopathies (NPHP-RC) have strong genotype and phenotype heterogeneity, and the transplantation strategy of Boichis syndrome is still controversial. Our purpose was to examine associations of genotype and phenotype in children with NPHP-RC and analyze the transplantation strategies of different phenotypes. METHODS: The records of children with NPHP treated at our center from 01/2018 to 03/2021 were retrospectively reviewed. Inclusion criteria were a diagnosis of NPHP, received kidney transplantation, and received whole exome sequencing (WES) or nephropathy gene panel testing. RESULTS: Twenty-nine children with NPHP were included. Nine children (31%) had NPHP1 mutations, and all presented with isolated nephropathy. Eighteen of 20 patients with non-NPHP1 mutations had compound heterozygous mutations, and 70% had extrarenal phenotype. Age at disease presentation (11.2 ± 1.94 years) and the development of kidney failure (12.4 ± 2.70 years) were later in children with NPHP1 mutations than those with non-NPHP1 mutations (5.2 ± 2.83 years and 5.7 ± 2.92 years, respectively). Four of six children with NPHP3 mutations were diagnosed with Boichis syndrome due to liver fibrosis. Isolated kidney transplantation resulted in good outcomes for patients with mild or moderate liver fibrosis without portal hypertension, while cholestasis was common postoperatively and could be resolved with ursodeoxycholic acid. CONCLUSIONS: NPHP1 mutations are the most common in children with NPHP, and the phenotype of NPHP1 mutation is significantly different from that of non-NPHP1 mutation. For NPHP patients with mild to moderate liver fibrosis without portal hypertension, timely treatment of cholestasis could prevent the rapid progression of liver function damage after isolated kidney transplantation. GRAPHICAL ABSTRACT: [Figure: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-022-05763-3. Springer Berlin Heidelberg 2022-10-13 2023 /pmc/articles/PMC10060285/ /pubmed/36227438 http://dx.doi.org/10.1007/s00467-022-05763-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Li, Jianyi Su, Xiaojun Zhang, Huanxi Wu, Wenrui Li, Jianming Chen, Yanxu Li, Jun Fu, Qian Wu, Chenglin Zhong, Xuhui Wang, Changxi Liu, Longshan Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP |
title | Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP |
title_full | Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP |
title_fullStr | Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP |
title_full_unstemmed | Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP |
title_short | Genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by NPHP |
title_sort | genotype and phenotype analysis and transplantation strategy in children with kidney failure caused by nphp |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060285/ https://www.ncbi.nlm.nih.gov/pubmed/36227438 http://dx.doi.org/10.1007/s00467-022-05763-3 |
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