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Nearly all hereditary paragangliomas in The Netherlands are caused by two founder mutations in the SDHD gene
Author(s) -
Taschner Peter E.M.,
Jansen Jeroen C.,
Baysal Bora E.,
Bosch Anne,
Rosenberg Efraim H.,
BröckerVriends Annette H.J.T.,
van der Mey Andel G.L.,
van Ommen GertJan B.,
Cornelisse Cees J.,
Devilee Peter
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.1144
Subject(s) - sdhd , paraganglioma , genetics , germline mutation , allele , biology , pheochromocytoma , gene , mutation , medicine , pathology , endocrinology
Hereditary paragangliomas or glomus tumors are usually benign slow‐growing tumors in the head and neck region. The inheritance pattern of hereditary paraganglioma is autosomal dominant with imprinting. Recently, we have identified the SDHD gene encoding subunit D of the mitochondrial respiratory chain complex II as one of the genes involved in hereditary paragangliomas. Here, we demonstrate that two founder mutations, Asp92Tyr and Leu139Pro, are responsible for paragangliomas in 24 and 6 of the 32 independently ascertained Dutch paraganglioma families, respectively. These two mutations were also detected among 20 of 55 isolated patients. Ten of the isolated patients had multiple paragangliomas, and in eight of these SDHD germline mutations were found, indicating that multicentricity is a strong predictive factor for the hereditary nature of the disorder in isolated patients. In addition, we demonstrate that the maternally derived wild‐type SDHD allele is lost in tumors from mutation‐carrying patients, indicating that SDHD functions as a tumor suppressor gene. © 2001 Wiley‐Liss, Inc.