{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:17Z","timestamp":1753869677861,"version":"3.41.2"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), caused by heterozygous germline pathogenic variants in the <jats:italic>FH<\/jats:italic>, confers an increased risk for cutaneous and uterine leiomyomas and renal cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>About 13,722 advanced cancer patients, including 560 with renal cell carcinoma, had germline analysis performed in the context of tumor\u2010normal sequencing under an IRB approved protocol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report two unrelated individuals with early onset kidney cancer who both carried the c.914C\u00a0&gt;\u00a0T (p.Phe305Ser) germline variant in the <jats:italic>FH<\/jats:italic>. 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This combination of evidence suggests that the <jats:italic>FH<\/jats:italic> c.914C\u00a0&gt;\u00a0T (p.Phe305Ser) is pathogenic for HLRCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1293","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T09:14:05Z","timestamp":1590657245000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fumarate hydratase c.914T\u00a0&gt;\u00a0C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-1564","authenticated-orcid":false,"given":"Kelsey 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