Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.−14C>T mutation in all patients
- Frank Rauch1,
- Pierre Moffatt1,
- Moira Cheung1,
- Peter Roughley1,
- Liljana Lalic1,
- Allan M Lund2,
- Norman Ramirez3,
- Somayyeh Fahiminiya4,
- Jacek Majewski4,
- Francis H Glorieux1
- 1Shriners Hospital for Children, Montreal, Quebec, Canada
- 2Center for Inherited Metabolic Disorders, Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark
- 3Pediatric Orthopedic Department, Mayaguez Medical Center, Mayaguez, Puerto Rico
- 4Department of Human Genetics, McGill University, Montreal, Quebec, Canada
- Correspondence to Dr Frank Rauch, Shriners Hospital for Children, 1529 Cedar, Montreal, H3G 1A6 Quebec, Canada;
- Received 15 September 2012
- Revised 18 October 2012
- Accepted 19 October 2012
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.