{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T12:12:16Z","timestamp":1792239136732,"version":"4.4.0"},"reference-count":45,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2011,1,6]]},"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder predisposing humans to cutaneous and uterine leiomyomas; in 20% of affected families, type 2 papillary renal cell cancers (PRCCII) also occur with aggressive course and poor prognosis. HLRCC results from heterozygous germline mutations in the tumour suppressor fumarate hydratase (\n                      <jats:italic>FH<\/jats:italic>\n                      ) gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      As part of the French National Cancer Institute (INCa) \u2018Inherited predispositions to kidney cancer\u2019 network, sequence analysis and a functional study of\n                      <jats:italic>FH<\/jats:italic>\n                      were preformed in 56 families with clinically proven or suspected HLRCC and in 23 patients with isolated PRCCII (5 familial and 18 sporadic).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The study identified 32 different germline\n                      <jats:italic>FH<\/jats:italic>\n                      mutations (15 missense, 6 frameshifts, 4 nonsense, 1 deletion\/insertion, 5 splice site, and 1 complete deletion) in 40\/56 (71.4%) families with proven or suspected HLRCC and in 4\/23 (17.4%) probands with PRCCII alone, including 2 sporadic cases. 21 of these were novel and all were demonstrated as deleterious by significant reduction of FH enzymatic activity. In addition, 5 asymptomatic parents in 3 families were confirmed as carrying disease-causing mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study identified and characterised 21 novel\n                      <jats:italic>FH<\/jats:italic>\n                      mutations and demonstrated that PRCCII can be the only one manifestation of HLRCC. Due to the incomplete penetrance of HLRCC, the authors propose to extend the\n                      <jats:italic>FH<\/jats:italic>\n                      mutation analysis to every patient with PRCCII occurring before 40\u2005years of age or when renal tumour harbours characteristic histologic features, in order to discover previously ignored HLRCC affected families.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg.2010.085068","type":"journal-article","created":{"date-parts":[[2011,3,13]],"date-time":"2011-03-13T19:27:54Z","timestamp":1300044474000},"page":"226-234","source":"Crossref","is-referenced-by-count":128,"title":["Novel\n                    <i>FH<\/i>\n                    mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell 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