title: Neurofibromatosis type 2 French cohort analysis using a comprehensive NF2 molecular diagnostic strategy.
abstract: OBJECTIVE
  Neurofibromatosis type 2 (NF2) affects about one in 25,000 to 40,000 people. Most NF2 patients have private loss-of-function mutations scattered along the NF2 gene. Here, we present our NF2 investigation strategy.
  
  
  METHODS
  We report a comprehensive NF2 mutation analysis of 221 NF2 French patients: 134 unrelated typical NF2 patients fulfilling the Manchester criteria and 87 unrelated patients presenting symptoms that partially fulfilled the Manchester criteria.
  
  
  RESULTS
  A NF2 mutation was identified in 56 of the 221 patients, giving a global mutation detection rate of 25%. This rate reached 37% (49/134) for typical NF2 patients fulfilling the Manchester criteria and only 8% (7/87) for patients presenting symptoms suggestive of NF2. Six of these seven patients were under 25 of age. Our approach showed that 77% of NF2 identified variants were detected by coding exons sequencing. Multiplex ligation-dependent probe amplification allowed the identification of restricted rearrangements (23% of NF2 identified variants corresponding to complete deletion or partial deletion/duplication of NF2).
  
  
  CONCLUSIONS
  High mutation detection rate can be achieved if well phenotyped NF2 patients are studied with multiple complementary and optimized techniques. NF2 somatic mosaicism detection was improved by frozen tumor samples molecular analysis.
authors.affiliation: EA7331, faculté de pharmacie de Paris, université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de biochimie et de génétique moléculaire, hôpital Cochin, AP-HP, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Pasmant
authors.affiliation: Service de biochimie et de génétique moléculaire, hôpital Cochin, AP-HP, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Louvrier
authors.affiliation: EA7331, faculté de pharmacie de Paris, université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de biochimie et de génétique moléculaire, hôpital Cochin, AP-HP, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Luscan
authors.affiliation: Service de biochimie et de génétique moléculaire, hôpital Cochin, AP-HP, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.affiliation: EA7331, faculté de pharmacie de Paris, université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Laurendeau
authors.affiliation: EA7331, faculté de pharmacie de Paris, université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de biochimie et de génétique moléculaire, hôpital Cochin, AP-HP, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Vidaud
authors.affiliation: EA7331, faculté de pharmacie de Paris, université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de biochimie et de génétique moléculaire, hôpital Cochin, AP-HP, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Vidaud
authors.affiliation: Service de neurochirurgie, hôpital Beaujon, AP-HP, Clichy, France.
authors.forename: S
authors.initials: S
authors.lastname: Goutagny
authors.affiliation: Service de neurochirurgie, hôpital Pitié-Salpétrière, AP-HP, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Kalamarides
authors.affiliation: EA7331, faculté de pharmacie de Paris, université Paris Descartes, Sorbonne Paris Cité, Paris, France; Service de biochimie et de génétique moléculaire, hôpital Cochin, AP-HP, Paris, France. Electronic address: beatrice.parfait@parisdescartes.fr.
authors.forename: B
authors.initials: B
authors.lastname: Parfait
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D016515:Genes, Neurofibromatosis 2 / Q000502:physiology*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D016518:Neurofibromatosis 2 / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D057089:Pathology, Molecular
keywords: Critères de Manchester; MLPA; Manchester criteria; Mosaïque somatique; Multiplex ligation-dependent probe amplification; NF2; Neurofibromatose de type 2; Neurofibromatosis type 2; Somatic mosaicism