{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:17:50Z","timestamp":1783487870798,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["no. 81770427"],"award-info":[{"award-number":["no. 81770427"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["no. 82070822"],"award-info":[{"award-number":["no. 82070822"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["nyaspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Fumarate hydratase (FH) catalyzes the conversion of fumaric acid to\n                    <jats:sc>L<\/jats:sc>\n                    \u2010malic acid. Heterozygous variants of the human fumarate hydratase gene (\n                    <jats:italic>FH<\/jats:italic>\n                    ) predispose to hereditary leiomyomatosis and renal cell cancer and, rarely, pheochromocytoma\/paraganglioma (PPGL). No mosaic variant in\n                    <jats:italic>FH<\/jats:italic>\n                    has been reported yet. Using next\u2010generation sequencing, five individuals with\n                    <jats:italic>FH<\/jats:italic>\n                    variants were found in 319 PPGL patients. Immunohistochemistry staining and loss of heterozygosity analysis in tumor tissues were performed to determine the pathogenicity of the variants. Deep targeted sequencing was performed on the peripheral blood DNA of a pheochromocytoma (PCC) patient with uterine leiomyomas. Finally, two of the five variants were found to be pathogenic. A germline variant (c.817G&gt;A, p.Ala273Thr) was found in a patient with a PPGL family history. A mosaic variant (c.206G&gt;A, p.Gly69Asp) with an allelic ratio of 5% in blood DNA was confirmed in the PCC patient with uterine leiomyomas. No metastatic PPGL was observed in the two PPGL patients with\n                    <jats:italic>FH<\/jats:italic>\n                    pathogenic variants. In summary, we report mosaicism in\n                    <jats:italic>FH<\/jats:italic>\n                    and the first PPGL pedigree with an\n                    <jats:italic>FH<\/jats:italic>\n                    pathogenic germline variant. Both germline variants\u00a0and mosaicism should be taken into account during genetic testing.\n                  <\/jats:p>","DOI":"10.1111\/nyas.14866","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:14:56Z","timestamp":1657671296000},"page":"262-270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fumarate hydratase gene germline variants and mosaicism associated with pheochromocytoma and paraganglioma"],"prefix":"10.1111","volume":"1516","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6415-3992","authenticated-orcid":false,"given":"Xiaosen","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology National Health Commission of the People's Republic of China Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunying","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology National Health Commission of the People's Republic of China Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinjie","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology National Health Commission of the People's Republic of China Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology National Health Commission of the People's Republic of China Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anli","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrinology National Health Commission of the People's Republic of China Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000634"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13014"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1659"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt639"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng849"},{"key":"e_1_2_9_7_1","first-page":"887","article-title":"Corrigendum: Inhibition of \u03b1\u2010KG\u2010dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors","volume":"29","author":"Xiao M.","year":"2015","journal-title":"Genes & 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