{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T06:27:26Z","timestamp":1776320846746,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,5,11]],"date-time":"2013-05-11T00:00:00Z","timestamp":1368230400000},"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":[[2013,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> mutations predispose carriers to hereditary paraganglioma syndrome. The objective of this study was to assess the genotype\u2013phenotype correlation of a large <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>utch cohort of <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> mutation carriers and evaluate potential differences in clinical phenotypes due to specific <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> gene mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Retrospective, descriptive single\u2010centre study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>All consecutive <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> mutation carriers followed at the <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>epartment of <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>ndocrinology of the <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>eiden <jats:styled-content style=\"fixed-case\">U<\/jats:styled-content>niversity <jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>edical <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>enter were included.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>Subjects were investigated according to structured protocols used for standard care, including repetitive biochemical and radiological screening for paragangliomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two hundred and one <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> mutation carriers with a mean age at presentation of 42\u00b76\u00a0\u00b1\u00a014\u00b74\u00a0years and a mean follow\u2010up of 5\u00b78\u00a0\u00b1\u00a05\u00b74\u00a0years were evaluated. Eighty\u2010one percent carried the <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> c.274<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>&gt;<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> (p.<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>sp92<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>yr) mutation and 13% the <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> c.416T&gt;C (p.<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>eu139<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>ro) mutation. No differences in clinical phenotype between these two specific <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> mutations were found. Ninety\u2010one percent developed one or multiple paragangliomas in the head and neck region (<jats:styled-content style=\"fixed-case\">HNPGL<\/jats:styled-content>s), of which the carotid body tumour was the most prevalent (85%). Eighteen carriers developed pheochromocytomas, fifteen sympathetic paragangliomas and nine carriers (4%) suffered from malignant paraganglioma. By end of follow\u2010up, sixteen <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> mutation carriers (8%) displayed no biochemical or radiological evidence of manifest disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The two main <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>utch <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> founder mutations do not differ in clinical expression. <jats:italic><jats:styled-content style=\"fixed-case\">SDHD<\/jats:styled-content><\/jats:italic> mutations are associated with the development of multiple <jats:styled-content style=\"fixed-case\">HNPGL<\/jats:styled-content>s and predominantly benign disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12223","type":"journal-article","created":{"date-parts":[[2013,4,16]],"date-time":"2013-04-16T03:51:13Z","timestamp":1366084273000},"page":"824-831","source":"Crossref","is-referenced-by-count":10,"title":["No difference in phenotype of the main <scp>D<\/scp>utch <i><scp>SDHD<\/scp><\/i> founder mutations"],"prefix":"10.1111","volume":"79","author":[{"given":"L. T.","family":"van Hulsteijn","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases Leiden University Medical Center Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. C.","family":"den Dulk","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases Leiden University Medical Center Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. J.","family":"Hes","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. P.","family":"Bayley","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. C.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department ofOtorhinolargyngology Leiden University Medical Center Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. P. 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