title: Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.-14C>T mutation in all patients.
abstract: BACKGROUND
  Osteogenesis imperfecta (OI) type V is an autosomal dominant bone fragility disorder that we had described a decade ago. Recent research has shown that OI type V is caused by a recurrent c.-14C>T mutation in IFITM5. In the present study, we assessed all patients diagnosed with OI type V at our institutions for the presence of the IFITM5 mutation.
  
  
  METHODS
  IFITM5 exon 1 was analysed by Sanger sequencing in genomic DNA from 42 patients with OI type V (age: 2-67 years; 18 female).
  
  
  RESULTS
  The c.-14C>T mutation of IFITM5 was detected in all individuals. Indicators of disease severity varied widely: Height z-scores (n=38) ranged from -8.7 to -0.1, median -3.5. Median final height was 147 cm in men (N=15) and 145 cm in women (N=10). Lumbar spine areal bone mineral density z-scores in the absence of bisphosphonate treatment (n=29) were between -7.7 and -0.7, median -5.3. Scoliosis was present in 57%, vertebral compression fractures in 90% of patients.
  
  
  CONCLUSIONS
  Even though the disease-causing mutation is identical among patients with OI type V, the interindividual phenotypic variability is considerable.
authors.affiliation: Shriners Hospital for Children, Montreal, Quebec, Canada. frauch@shriners.mcgill.ca
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
authors.forename: Pierre
authors.initials: P
authors.lastname: Moffatt
authors.forename: Moira
authors.initials: M
authors.lastname: Cheung
authors.forename: Peter
authors.initials: P
authors.lastname: Roughley
authors.forename: Liljana
authors.initials: L
authors.lastname: Lalic
authors.forename: Allan M
authors.initials: AM
authors.lastname: Lund
authors.forename: Norman
authors.initials: N
authors.lastname: Ramirez
authors.forename: Somayyeh
authors.initials: S
authors.lastname: Fahiminiya
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.forename: Francis H
authors.initials: FH
authors.lastname: Glorieux
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D011859:Radiography; D055815:Young Adult
chemical_list: C575746:IFITM5 protein, human; D008565:Membrane Proteins