Open AccessFumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome
Author(s) -
Breen Kelsey E.,
Carlo Maria I.,
Kemel Yelena,
Maio Anna,
Chen YingBei,
Zhang Liying,
CeyhanBirsoy Ozge,
Mandelker Diana
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1293
Subject(s) - leiomyomatosis , medicine , germline , context (archaeology) , proband , kidney cancer , cancer , pathology , germline mutation , fumarase , renal cell carcinoma , leiomyoma , mutation , biology , genetics , paleontology , gene
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.