title: Search for copy number alterations in the MEFV gene using multiplex ligation probe amplification, experience from three diagnostic centres.
abstract: Familial mediterranean fever (FMF) is a hereditary autoinflammatory autosomal recessive disease caused by mutations in the MEFV gene. Despite the identification of many disease associated MEFV mutations, often the clinical diagnosis cannot be genetically confirmed. The currently used diagnostic sequencing techniques only allow the detection of point mutations, small deletions or duplications. The question as to whether larger genetic alterations are also involved in the pathophysiology of FMF remains to be answered. To address this question, we used multiplex ligation-dependent probe amplification (MLPA) on a total of 216 patients with FMF symptoms. This careful analysis revealed that not a single deletion/duplication could be detected in this large cohort of patients. This result suggests that single or multiexon MEFV gene copy number changes do not contribute substantially, if at all, to the MEFV mutation spectrum.
authors.affiliation: DBG Department of Medical Genetics, UMC Utrecht, The Netherlands. m.e.vangijn@umcutrecht.nl
authors.forename: Marielle E
authors.initials: ME
authors.lastname: van Gijn
authors.forename: Stéphan
authors.initials: S
authors.lastname: Soler
authors.forename: Claire
authors.initials: C
authors.lastname: de la Chapelle
authors.forename: Marcel
authors.initials: M
authors.lastname: Mulder
authors.forename: Cécile
authors.initials: C
authors.lastname: Ritorre
authors.forename: Marjolein
authors.initials: M
authors.lastname: Kriek
authors.forename: Laurent
authors.initials: L
authors.lastname: Philibert
authors.forename: Michiel
authors.initials: M
authors.lastname: van der Wielen
authors.forename: Joost
authors.initials: J
authors.lastname: Frenkel
authors.forename: Sylvie
authors.initials: S
authors.lastname: Grandemange
authors.forename: Egbert
authors.initials: E
authors.lastname: Bakker
authors.forename: Johannes K
authors.initials: JK
authors.lastname: Ploos van Amstel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Touitou
mesh_terms: D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000235:genetics*; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D006801:Humans; D022521:Ligase Chain Reaction; D008297:Male; D017354:Point Mutation; D000071198:Pyrin
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin