{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T22:50:57Z","timestamp":1761519057045},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,1,25]],"date-time":"2013-01-25T00:00:00Z","timestamp":1359072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Germline mutations in four genes (<jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> VHL<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> SDHB<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content>) are detected in about 17% of patients with apparently sporadic pheochromocytoma. Thus, genetic screening of all patients with this disease is suggested for a rational diagnostic approach and management.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To report the clinical, biochemical and genetic analysis of three unrelated patients affected by pheochromocytoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and patients<\/jats:title><jats:p>All the coding regions and exon\u2013intron boundaries of <jats:italic><jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">SDHB<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> genes were sequenced in three unrelated patients with intra\u2010adrenal pheochromocytoma: a 17\u2010year\u2010old girl, a 15\u2010year\u2010old boy and a 73\u2010year\u2010old man. The family history of all three cases was negative for von <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>ippel\u2013<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>indau lesions or other types of endocrine tumours. Structural modelling of the <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content> protein was then performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel germline <jats:italic><jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content><\/jats:italic> gene point mutation, a <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> nucleotide substitution in exon 3, leading to an aspartate to asparagine amino acid change in codon 197 (<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>197<jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>). No mutations were found in <jats:italic><jats:styled-content style=\"fixed-case\">RET<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">SDHB<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> genes. Structural modelling of the <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content> protein suggests that the <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>197<jats:styled-content style=\"fixed-case\">N<\/jats:styled-content> mutation could have a functional role.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study expands the number of <jats:italic><jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content><\/jats:italic> gene known mutations and indicates the usefulness of performing the genetic analysis in all patients with apparently sporadic pheochromocytoma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12032","type":"journal-article","created":{"date-parts":[[2012,9,5]],"date-time":"2012-09-05T08:05:08Z","timestamp":1346832308000},"page":"391-397","source":"Crossref","is-referenced-by-count":5,"title":["A new germline <i><scp>VHL<\/scp><\/i> gene mutation in three patients with apparently sporadic 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