title: SDH mutations in patients affected by paraganglioma syndromes: a personal experience.
abstract: Mutations in genes encoding mitochondrial succinate dehydrogenase (SDH) are frequently involved in the development of neural crest-derived (NCD) tumors, such as pheochromocytomas (PHEOs) or paragangliomas (PGLs). In this study we report the results of sequencing analysis in leukocyte DNA of patients affected by PHEO/PGL who turned out to be SDH mutation carriers. A nonsense germline heterozygous mutation (Q109X) was found in the exon 4 of the SDHD gene in the index cases of six unrelated families affected by PHEO/PGL. Haplotype analysis showed the presence of a founder effect. Affected patients showed high clinical variability, ranging from monolateral to bilateral glomus tumors, variably associated or not with PGLs or PHEOs. A novel missense SDHD variant, T112I, was also found in one of our families. A new missense G106D mutation, involving a highly conserved amino acid, was found in two sisters affected by bilateral glomus tumors. A P81L mutation associated with abdominal and head and neck PGL was detected in three families. A G12S variant of the SDHD gene was found in one patient affected by a PHEO. The finding of this variant in 3 of 100 control subjects suggests that it is a polymorphism and not a mutation. A novel IVS2-1G>T variant was found at intron 2 of SDHD gene in one patient affected by a glomus tumor. All the tumors associated with SDHD mutations were benign. Conversely, the only mutation we found in SDHB gene (IVS3+1G>A) was associated with a malignant PHEO.
authors.affiliation: Endocrinology Section, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6 50139, Florence, and Internal Medicine 2, Pistoia Hospital, Italy. m.mannelli@dfc.unifi.it
authors.forename: M
authors.initials: M
authors.lastname: Mannelli
authors.forename: L
authors.initials: L
authors.lastname: Simi
authors.forename: T
authors.initials: T
authors.lastname: Ercolino
authors.forename: M S
authors.initials: MS
authors.lastname: Gaglianò
authors.forename: L
authors.initials: L
authors.lastname: Becherini
authors.forename: S
authors.initials: S
authors.lastname: Vinci
authors.forename: R
authors.initials: R
authors.lastname: Sestini
authors.forename: F
authors.initials: F
authors.lastname: Gensini
authors.forename: P
authors.initials: P
authors.lastname: Pinzani
authors.forename: M
authors.initials: M
authors.lastname: Mascalchi
authors.forename: L
authors.initials: L
authors.lastname: Guerrini
authors.forename: C
authors.initials: C
authors.lastname: Pratesi
authors.forename: G
authors.initials: G
authors.lastname: Nesi
authors.forename: F
authors.initials: F
authors.lastname: Torti
authors.forename: F
authors.initials: F
authors.lastname: Cipollini
authors.forename: G P
authors.initials: GP
authors.lastname: Bernini
authors.forename: M
authors.initials: M
authors.lastname: Genuardi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D010235:Paraganglioma / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013385:Succinate Dehydrogenase / Q000737:chemistry / Q000235:genetics*
chemical_list: D013385:Succinate Dehydrogenase