title: A novel mutation in the SDHD gene responsible for familial paraganglioma. Medical and psychological implications.
abstract: Familial paragangliomas/pheochromocytomas are dominantly inherited disorders characterized by the development of highly vascularized tumors of the head and neck, derived from non-chromaffin cells of the extra-adrenal paraganglia, and tumors with endocrine activity, derived from chromaffin cells, usually located in the adrenal medulla and pre- and para-vertebral thoracoabdominal regions. Germline inactivating heterozygous mutations in one of the genes encoding for succinate dehydrogenase subunits B, C or D (SDHB, SDHC or SDHD) are responsible for hereditary paragangliomas (PGLs), accounting for nearly 70% of familial cases. Particularly in the SDHD gene, different types of mutations have been found, nevertheless, alterations other than point mutations and deletion leading to missense/nonsense/splicing mutations are extremely rare. Here we report a family with multiple cases of PGL which co-segregates with a novel SDHD gene mutation predictable to give rise to an abnormal gene product (CybS). The identification of the molecular event responsible for PGL in our family made genetic counseling particularly useful for younger first degree relatives at risk to develop this late-onset disease.
authors.affiliation: Center of Medical Genetics, Dept. of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. pprontera@hotmail.com
authors.forename: P
authors.initials: P
authors.lastname: Prontera
authors.forename: B
authors.initials: B
authors.lastname: Ferrando
authors.forename: V
authors.initials: V
authors.lastname: Giuliani
authors.forename: F
authors.initials: F
authors.lastname: Falcinelli
authors.forename: A
authors.initials: A
authors.lastname: Mencarelli
authors.forename: D
authors.initials: D
authors.lastname: Rogaia
authors.forename: B
authors.initials: B
authors.lastname: Pasini
authors.forename: E
authors.initials: E
authors.lastname: Donti
mesh_terms: D002345:Carotid Body Tumor / Q000098:blood supply / Q000235:genetics / Q000523:psychology; D002533:Cerebral Angiography; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D018703:Founder Effect; D020440:Gene Duplication; D006580:Genetic Carrier Screening; D005817:Genetic Counseling / Q000523:psychology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D009378:Neoplasms, Multiple Primary / Q000098:blood supply / Q000235:genetics / Q000523:psychology; D010235:Paraganglioma / Q000098:blood supply / Q000235:genetics* / Q000523:psychology; D010236:Paraganglioma, Extra-Adrenal / Q000098:blood supply / Q000235:genetics / Q000523:psychology; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: D018389:Codon, Nonsense; C491545:SDHD protein, human; D013385:Succinate Dehydrogenase