title: Autosomal dominant familial Mediterranean fever in Northern European Caucasians associated with deletion of p.M694 residue-a case series and genetic exploration.
abstract: This study was undertaken to characterize the phenotype and response to treatment in patients with autosomal dominant FMF caused by MEFV p.M694del mutation and to use haplotype reconstruction to investigate the possibility of common ancestry.
  
  
  
  MEFV gene was analysed in 3500 subjects with suspected FMF referred to a single UK centre between 2002 and 2014. Patients with p.M694del underwent additional screening of the SAA1 gene as well as haplotype reconstruction of the MEFV locus.
  
  
  
  The p.M694del variant was identified in 21 patients, sharing an identical disease haplotype that appears to have arisen about 550 years ago. The SAA1.1 allele was found in four patients, including two with AA amyloidosis. The clinical features comprised typical FMF symptoms with median age at onset of 18 years; three patients presented with AA amyloidosis, of whom two had had symptoms of FMF in retrospect. Fifteen patients had received colchicine treatment, all with excellent responses.
  
  
  
  The p.M694del variant is associated with autosomal dominantly inherited FMF in Northern European Caucasians. Symptoms may develop later in life than in classical recessive FMF but are otherwise similar, as is the response to colchicine treatment. The 14% incidence of AA amyloidosis may reflect delay in diagnosis associated with extreme rarity of FMF in this population. The common haplotype suggests a single founder living in about 1460.
authors.affiliation: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, University College London Medical School, London, UK d.rowczenio@ucl.ac.uk.
authors.forename: Dorota M
authors.initials: DM
authors.lastname: Rowczenio
authors.affiliation: Centre for Nephrology, University College London, London, UK.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Iancu
authors.affiliation: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, University College London Medical School, London, UK.
authors.forename: Hadija
authors.initials: H
authors.lastname: Trojer
authors.affiliation: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, University College London Medical School, London, UK.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Gilbertson
authors.affiliation: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, University College London Medical School, London, UK.
authors.forename: Julian D
authors.initials: JD
authors.lastname: Gillmore
authors.affiliation: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, University College London Medical School, London, UK.
authors.forename: Ashutosh D
authors.initials: AD
authors.lastname: Wechalekar
authors.affiliation: Centre for Nephrology, University College London, London, UK.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tekman
authors.affiliation: Centre for Nephrology, University College London, London, UK.
authors.forename: Horia C
authors.initials: HC
authors.lastname: Stanescu
authors.affiliation: Centre for Nephrology, University College London, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Kleta
authors.affiliation: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, University College London Medical School, London, UK.
authors.forename: Thirusha
authors.initials: T
authors.lastname: Lane
authors.affiliation: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, University College London Medical School, London, UK.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
authors.affiliation: National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, University College London Medical School, London, UK.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Lachmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000235:genetics; D002648:Child; D003078:Colchicine / Q000627:therapeutic use; D010505:Familial Mediterranean Fever / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009404:Nephrotic Syndrome / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000071198:Pyrin / Q000235:genetics*; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism; D050257:Tubulin Modulators / Q000627:therapeutic use; D006113:United Kingdom; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C000604192:MEFV protein, human; D000071198:Pyrin; C521404:SAA1 protein, human; D000685:Serum Amyloid A Protein; D050257:Tubulin Modulators; D003078:Colchicine
keywords: AA amyloidosis; FMF; MEFV gene; colchicine; dominant inheritance; haplotype