Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation
Gitelman syndrome is a rare, recessively inherited disease characterized by chronic hypokalemia and hypomagnesemia as a result of defective electrolyte co-transport at the level of the distal convoluted tubule of the kidney. Here, we present the first report of a patient with Gitelman syndrome who d...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2021
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| Online Access: | https://hdl.handle.net/10356/146678 |
| _version_ | 1811690252256935936 |
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| author | Chan, Jason Yongsheng Toh, Ming Ren Chong, Siao Ting Nur Diana Ishak Kolinjivadi, Arun Mouli Chan, Sock Hoai Lee, Elizabeth Boot, Arnoud Shao-Tzu, Li Chew, Min-Hoe Ngeow, Joanne |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Chan, Jason Yongsheng Toh, Ming Ren Chong, Siao Ting Nur Diana Ishak Kolinjivadi, Arun Mouli Chan, Sock Hoai Lee, Elizabeth Boot, Arnoud Shao-Tzu, Li Chew, Min-Hoe Ngeow, Joanne |
| author_sort | Chan, Jason Yongsheng |
| collection | NTU |
| description | Gitelman syndrome is a rare, recessively inherited disease characterized by chronic hypokalemia and hypomagnesemia as a result of defective electrolyte co-transport at the level of the distal convoluted tubule of the kidney. Here, we present the first report of a patient with Gitelman syndrome who developed multiple neoplasia including colorectal polyposis, synchronous colorectal cancers, recurrent breast fibroadenomata and a desmoid tumor. Whole-exome sequencing confirmed germline compound heterozygous mutations of c.179C > T and c.1326C > G in SLC12A3, and in addition, identified a monoallelic germline c.934-2A > G splice site mutation in MUTYH. In vitro, magnesium deficiency potentiated oxidative DNA damage in lymphoblastoid cell lines derived from the same patient. We postulate that monoallelic MUTYH mutations may manifest in the presence of cooperative non-genetic mechanisms, in this case possibly magnesium deficiency from Gitelman syndrome. |
| first_indexed | 2024-10-01T06:01:02Z |
| format | Journal Article |
| id | ntu-10356/146678 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:01:02Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1466782023-03-05T16:48:50Z Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation Chan, Jason Yongsheng Toh, Ming Ren Chong, Siao Ting Nur Diana Ishak Kolinjivadi, Arun Mouli Chan, Sock Hoai Lee, Elizabeth Boot, Arnoud Shao-Tzu, Li Chew, Min-Hoe Ngeow, Joanne Lee Kong Chian School of Medicine (LKCMedicine) Institute of Molecular and Cellular Biology, A*STAR Science::Medicine Cancer Genetics Genetics Research Gitelman syndrome is a rare, recessively inherited disease characterized by chronic hypokalemia and hypomagnesemia as a result of defective electrolyte co-transport at the level of the distal convoluted tubule of the kidney. Here, we present the first report of a patient with Gitelman syndrome who developed multiple neoplasia including colorectal polyposis, synchronous colorectal cancers, recurrent breast fibroadenomata and a desmoid tumor. Whole-exome sequencing confirmed germline compound heterozygous mutations of c.179C > T and c.1326C > G in SLC12A3, and in addition, identified a monoallelic germline c.934-2A > G splice site mutation in MUTYH. In vitro, magnesium deficiency potentiated oxidative DNA damage in lymphoblastoid cell lines derived from the same patient. We postulate that monoallelic MUTYH mutations may manifest in the presence of cooperative non-genetic mechanisms, in this case possibly magnesium deficiency from Gitelman syndrome. National Medical Research Council (NMRC) Published version This work was supported by the National Medical Research Council of Singapore, SingHealth Foundation, as well as the SingHealth Duke-NUS Academic Medical Centre and Oncology ACP. 2021-03-04T08:30:17Z 2021-03-04T08:30:17Z 2020 Journal Article Chan, J. Y., Toh, M. R., Chong, S. T., Nur Diana Ishak, Kolinjivadi, A. M., Chan, S. H., . . . Ngeow, J. (2020). Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation. npj Genomic Medicine, 5(1), 39-. doi:10.1038/s41525-020-00146-9 2056-7944 0000-0002-4801-3703 0000-0002-9002-350X 0000-0002-7717-7416 0000-0003-1558-3627 https://hdl.handle.net/10356/146678 10.1038/s41525-020-00146-9 33024574 2-s2.0-85091195244 1 5 en npj Genomic Medicine © 2020 The Author(s). This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visithttp://creativecommons.org/licenses/by/4.0/. application/pdf |
| spellingShingle | Science::Medicine Cancer Genetics Genetics Research Chan, Jason Yongsheng Toh, Ming Ren Chong, Siao Ting Nur Diana Ishak Kolinjivadi, Arun Mouli Chan, Sock Hoai Lee, Elizabeth Boot, Arnoud Shao-Tzu, Li Chew, Min-Hoe Ngeow, Joanne Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation |
| title | Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation |
| title_full | Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation |
| title_fullStr | Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation |
| title_full_unstemmed | Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation |
| title_short | Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation |
| title_sort | multiple neoplasia in a patient with gitelman syndrome harboring germline monoallelic mutyh mutation |
| topic | Science::Medicine Cancer Genetics Genetics Research |
| url | https://hdl.handle.net/10356/146678 |
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