Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome Journal Article
| Authors: | Breen, K. E.; Carlo, M. I.; Kemel, Y.; Maio, A.; Chen, Y. B.; Zhang, L.; Ceyhan-Birsoy, O.; Mandelker, D. |
| Article Title: | Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome |
| Abstract: | Background: Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), caused by heterozygous germline pathogenic variants in the FH, confers an increased risk for cutaneous and uterine leiomyomas and renal cancer. Methods: About 13,722 advanced cancer patients, including 560 with renal cell carcinoma, had germline analysis performed in the context of tumor-normal sequencing under an IRB approved protocol. Results: We report two unrelated individuals with early onset kidney cancer who both carried the c.914C > T (p.Phe305Ser) germline variant in the FH. Both tumors exhibited loss of FH staining by immunohistochemistry and/or positive 2SC staining. Subsequent familial testing discovered that a daughter of a proband who carried the variant had both cutaneous and uterine leiomyomas. Conclusion: This combination of evidence suggests that the FH c.914C > T (p.Phe305Ser) is pathogenic for HLRCC. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC |
| Keywords: | mutation; carcinoma; leiomyomatosis; renal cell; fumarate hydratase |
| Journal Title: | Molecular Genetics and Genomic Medicine |
| Volume: | 8 |
| Issue: | 8 |
| ISSN: | 2324-9269 |
| Publisher: | John Wiley & Sons Ltd. |
| Date Published: | 2020-08-01 |
| Start Page: | e1293 |
| Language: | English |
| DOI: | 10.1002/mgg3.1293 |
| PUBMED: | 32463173 |
| PROVIDER: | scopus |
| PMCID: | PMC7434728 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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