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J Med Genet 50:21-24 doi:10.1136/jmedgenet-2012-101307
  • Genotype-phenotype correlations

Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.−14C>T mutation in all patients

  1. Francis H Glorieux1
  1. 1Shriners Hospital for Children, Montreal, Quebec, Canada
  2. 2Center for Inherited Metabolic Disorders, Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark
  3. 3Pediatric Orthopedic Department, Mayaguez Medical Center, Mayaguez, Puerto Rico
  4. 4Department of Human Genetics, McGill University, Montreal, Quebec, Canada
  1. Correspondence to Dr Frank Rauch, Shriners Hospital for Children, 1529 Cedar, Montreal, H3G 1A6 Quebec, Canada; frauch{at}shriners.mcgill.ca
  • Received 15 September 2012
  • Revised 18 October 2012
  • Accepted 19 October 2012

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.