title: Mutation analysis of the SDHD gene in four kindreds with familial paraganglioma: description of one novel germline mutation.
abstract: The familial paraganglioma syndrome is an autosomal dominant disorder characterized by the presence of carotid body paragangliomas and, less frequently, paragangliomas of the glomus jugulare, glomus vagale, and adrenal pheochromocytomas. Germline mutations of the genes for succinate dehydrogenase subunits D, B, or C (SDHD, SDHB, SDHC) have been identified in some kindreds with familial paraganglioma. In this study, we report the clinicopathologic features of four different kindreds with familial paraganglioma, which were screened for germline mutations in the SDHD gene. DNA was obtained from tumor and normal tissue, as well as from peripheral blood. Mutation analysis was performed by single-strand conformation polymorphism analysis and DNA sequencing. SDHD germline mutations were detected in the affected family members of the four families, as well as in several asymptomatic carriers. An identical mutation in exon 4 of SDHD (334-337delACTG) was identified in two apparently unrelated kindreds. The third family showed a germline mutation in exon 2 (W43X). The mutations present in these three families had been previously described in Spanish families, suggesting a founder effect. The fourth family exhibited a mutation in exon 2 of SDHD (170-171delTT), which had not been previously identified. The affected family members of the four kindreds showed paragangliomas, located in the head and neck region, and all of them were benign. These results confirm that genetic testing of SDHD may be a powerful tool for the identification of the syndrome in patients with multiple or bilateral paragangliomas.
authors.affiliation: Department of Otorhinolaryngology, Hospital Universitari Arnau de Vilanova, University of Lleida, Lleida, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Velasco
authors.forename: Victor
authors.initials: V
authors.lastname: Palomar-Asenjo
authors.forename: Laura
authors.initials: L
authors.lastname: Gañan
authors.forename: Lluis
authors.initials: L
authors.lastname: Catasus
authors.forename: Nuria
authors.initials: N
authors.lastname: Llecha
authors.forename: Angel
authors.initials: A
authors.lastname: Panizo
authors.forename: Victor
authors.initials: V
authors.lastname: Palomar-Garcia
authors.forename: Miquel
authors.initials: M
authors.lastname: Quer
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
mesh_terms: D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010235:Paraganglioma / Q000235:genetics*; D010375:Pedigree; D010524:Peripheral Nervous System Neoplasms / Q000235:genetics*; D013030:Spain; D013385:Succinate Dehydrogenase
chemical_list: D008565:Membrane Proteins; C491545:SDHD protein, human; D013385:Succinate Dehydrogenase