title: Comprehensive mutation scanning of NF1 in apparently sporadic cases of pheochromocytoma.
abstract: BACKGROUND
  Pheochromocytoma is a rare manifestation in patients with neurofibromatosis type 1 (NF 1). The 57-exon susceptibility gene NF1 has so far not been systematically scanned for unexpected germline mutations in individuals with sporadic pheochromocytoma.
  
  
  METHODS
  Twenty-seven patients with bilateral adrenal and/or extraadrenal abdominal pheochromocytoma not carrying germline mutations of the genes VHL, RET, SDHB, and SDHD were selected from the European-American pheochromocytoma registry. All 57 exons and flanking intronic regions of the NF1 gene were PCR amplified using newly designed primer pairs to exclude the amplification of pseudogenes. Intragenic mutation scanning was performed using denaturing HPLC and bidirectional direct sequencing.
  
  
  RESULTS
  Of the 27 apparently sporadic cases, one (4%) was found to have a pathogenic germline NF1 mutation, Leu303Arg. Clinical reevaluation of this individual, who had bilateral pheochromocytoma, revealed classic, but very mild, features of NF 1, one cutaneous neurofibroma, axillary freckling, and Lisch nodules of the iris as well as a few café-au-lait spots.
  
  
  CONCLUSIONS
  In the absence of germline mutations in VHL, RET, SDHD, and SDHB, patients with pheochromocytoma, especially with bilateral disease, should be checked thoroughly for clinical lesions suggestive of underlying syndromes such as the cutaneous and ophthalmological features characteristic of NF 1.
authors.affiliation: Medizinische Universitätsklinik, Hugstetter Strasse 55, D 79106 Freiburg, Germany.
authors.forename: Birke
authors.initials: B
authors.lastname: Bausch
authors.forename: Ann-Cathrin
authors.initials: AC
authors.lastname: Koschker
authors.forename: Martin
authors.initials: M
authors.lastname: Fassnacht
authors.forename: Johanna
authors.initials: J
authors.lastname: Stoevesandt
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.forename: Hartmut P H
authors.initials: HP
authors.lastname: Neumann
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D002648:Child; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm