title: Novel SDHD germ-line mutations in pheochromocytoma patients.
abstract: BACKGROUND
  SDHD germ-line mutations predispose to pheochromocytoma (PCC) and paraganglioma (PGL).
  
  
  METHODS
  The incidence and types of SDHD germ-line mutations are determined in 70 patients with apparently sporadic adrenal and extra-adrenal PCC.
  
  
  RESULTS
  SDHD sequence variants were identified in the germ line of five patients. Two of three novel mutations were in exon 1 and one in exon 3. One patient had a codon 1 missense mutation (M1K) and a concurrent 3-bp deletion in intron 1. Three of 10 family members had only the exon 1 mutation, whereas one had only the intron 1 mutation. The other exon 1 mutation resulted from a deletion of nucleotides 28-33 with a 12-bp in-frame insertion (c.28_33 del ins TAGGAGGCCCTA). This mutation generated a premature stop codon after codon 9 and was also present in the brother who had a bilateral PCC. The third patient with a carotid body tumour, with an abdominal and a thoracic PGL had a 12-bp deletion in exon 3 (codons 91-94, c.271_282 del). Her father carried the same mutation and had bilateral carotid body tumours. Two further patients, one with six PGL, carried a previously described H50R polymorphism, whose disease-specific relevance is currently unclear. The three patients with bona fide SDHD mutations were younger than those without germ-line mutations.
  
  
  CONCLUSIONS
  SDHD germ-line mutations are rare in patients with PCC, but their identification is an important prerequisite for the clinical care and appropriate management of affected individuals and their families.
authors.affiliation: Section of Endocrine Surgery, Division of General Surgery, Medical University, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Neumayer
authors.forename: A
authors.initials: A
authors.lastname: Moritz
authors.forename: R
authors.initials: R
authors.lastname: Asari
authors.forename: A
authors.initials: A
authors.lastname: Weinhäusel
authors.forename: T
authors.initials: T
authors.lastname: Hölzenbein
authors.forename: G
authors.initials: G
authors.lastname: Kretschmer
authors.forename: B
authors.initials: B
authors.lastname: Niederle
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics; D010673:Pheochromocytoma / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: C491545:SDHD protein, human; D013385:Succinate Dehydrogenase