The IFITM5 mutation c.-14C-gt;?T results in an elongated transcript expressed in human bone; and causes varying phenotypic severity of osteogenesis imperfecta type V

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• 作者：Syndia Lazarus (1) (2) (3)
  Aideen M McInerney-Leo (1)
  Fiona A McKenzie (4) (5)
  Gareth Baynam (4) (5)
  Stephanie Broley (4)
  Barbra V Cavan (6)
  Craig F Munns (7) (8)
  Johannes Egbertus Hans Pruijs (9)
  David Sillence (10) (8)
  Paulien A Terhal (11)
  Karena Pryce (1)
  Matthew A Brown (1)
  Andreas Zankl (1) (2)
  Gethin Thomas (1)
  Emma L Duncan (1) (2) (3)
  
• 关键词：Osteogenesis imperfecta ; Interferon ; induced transmembrane protein 5 (IFITM5) ; Bone ; restricted interferon ; induced transmembrane protein ; like protein (BRIL) ; Hyperplastic callus ; Radial head dislocation
• 刊名：BMC Musculoskeletal Disorders
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：15
• 期：1
• 全文大小：193 KB
• 参考文献：1. Battle WH, Shattock SG: A remarkable case of diffuse cancellous osteoma of the femur, following a fracture, in which similar growths afterwards developed in connection with other bones. / Proc R Soc Med 1908,1(Pathol Sect):83-15.
  2. Smith R, Francis MJO, Houghton GR: / The Brittle Bone Syndrome. Osteogenesis Imperfecta. London: Butterworths; 1983.
  3. Bauze RJ, Smith R, Francis MJ: A new look at osteogenesis imperfecta. A clinical, radiological and biochemical study of forty-two patients. / J Bone Joint Surg (Br) 1975,57(1):2-2.
  4. Glorieux FH, Rauch F, Plotkin H, Ward L, Travers R, Roughley P, Lalic L, Glorieux DF, Fassier F, Bishop NJ: Type V osteogenesis imperfecta: a new form of brittle bone disease. / J Bone Miner Res 2000,15(9):1650-658. CrossRef
  5. Lee DY, Cho TJ, Choi IH, Chung CY, Yoo WJ, Kim JH, Park YK: Clinical and radiological manifestations of osteogenesis imperfecta type V. / J Korean Med Sci 2006,21(4):709-14. CrossRef
  6. Cheung MS, Glorieux FH, Rauch F: Natural history of hyperplastic callus formation in osteogenesis imperfecta type V. / J Bone Miner Res 2007,22(8):1181-186. CrossRef
  7. Fleming F, Woodhead HJ, Briody JN, Hall J, Cowell CT, Ault J, Kozlowski K, Sillence DO: Cyclic bisphosphonate therapy in osteogenesis imperfecta type V. / J Paediatr Child Health 2005,41(3):147-51. CrossRef
  8. Zeitlin L, Rauch F, Travers R, Munns C, Glorieux FH: The effect of cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta type V. / Bone 2006,38(1):13-0. CrossRef
  9. Cho TJ, Lee KE, Lee SK, Song SJ, Kim KJ, Jeon D, Lee G, Kim HN, Lee HR, Eom HH, Lee ZH, Kim OH, Park WY, Park SS, Ikegawa S, Yoo WJ, Choi IH, Kim JW: A single recurrent mutation in the 5-UTR of IFITM5 causes osteogenesis imperfecta type V. / Am J Hum Genet 2012,91(2):343-48. CrossRef
  10. Semler O, Garbes L, Keupp K, Swan D, Zimmermann K, Becker J, Iden S, Wirth B, Eysel P, Koerber F, Schoenau E, Bohlander SK, Wollnik B, Netzer C: A mutation in the 5-UTR of IFITM5 creates an in-frame start codon and causes autosomal-dominant osteogenesis imperfecta type V with hyperplastic callus. / Am J Hum Genet 2012,91(2):349-57. CrossRef
  11. Moffatt P, Gaumond MH, Salois P, Sellin K, Bessette MC, Godin E, de Oliveira PT, Atkins GJ, Nanci A, Thomas G: Bril: a novel bone-specific modulator of mineralization. / J Bone Miner Res 2008,23(9):1497-508. CrossRef
  12. Rauch F, Moffatt P, Cheung M, Roughley P, Lalic L, Lund AM, Ramirez N, Fahiminiya S, Majewski J, Glorieux FH: Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.-14C-gt;?T mutation in all patients. / J Med Genet 2013,50(1):21-4. CrossRef
  13. Shapiro JR, Lietman C, Grover M, Lu JT, Nagamani SC, Dawson BC, Baldridge DM, Bainbridge MN, Cohn DH, Blazo M, Roberts TT, Brennen FS, Wu Y, Gibbs RA, Melvin P, Campeau PM, Lee BH: Phenotypic variability of osteogenesis imperfecta type V caused by an IFITM5 mutation. / J Bone Miner Res 2013,28(7):1523-530. CrossRef
  14. Balasubramanian M, Parker MJ, Dalton A, Giunta C, Lindert U, Peres LC, Wagner BE, Arundel P, Offiah A, Bishop NJ: Genotype-phenotype study in type V osteogenesis imperfecta. / Clin Dysmorphol 2013,22(3):93-01. CrossRef
  15. Takagi M, Sato S, Hara K, Tani C, Miyazaki O, Nishimura G, Hasegawa T: A recurrent mutation in the 5-UTR of IFITM5 causes osteogenesis imperfecta type V. / Am J Med Genet A 2013,161A(8):1980-982. CrossRef
  16. Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS: A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. / Nat Genet 2006,38(5):525-27. CrossRef
  17. Grover M, Campeau PM, Lietman CD, Lu JT, Gibbs RA, Schlesinger AE, Lee BH: Osteogenesis imperfecta without features of type V caused by a mutation in the IFITM5 gene. / J Bone Miner Res 2013,28(11):2333-337. CrossRef
  18. Fassier AM, Rauch F, Aarabi M, Janelle C, Fassier F: Radial head dislocation and subluxation in osteogenesis imperfecta. / J Bone Joint Surg Am 2007,89(12):2694-704. CrossRef
  19. Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M, Mortier G, Mundlos S, Nishimura G, Rimoin DL, Robertson S, Savarirayan R, Sillence D, Spranger J, Unger S, Zabel B, Superti-Furga A: Nosology and classification of genetic skeletal disorders: 2010 revision. / Am J Med Genet A 2011,155A(5):943-68. CrossRef
  20. Sillence DO, Senn A, Danks DM: Genetic heterogeneity in osteogenesis imperfecta. / J Med Genet 1979,16(2):101-16. CrossRef
  21. Van Dijk FS, Pals G, Van Rijn RR, Nikkels PG, Cobben JM: Classification of osteogenesis imperfecta revisited. / Eur J Med Genet 2010,53(1):1-. CrossRef
  22. Forlino A, Cabral WA, Barnes AM, Marini JC: New perspectives on osteogenesis imperfecta. / Nat Rev Endocrinol 2011,7(9):540-57. CrossRef
  23. Daley E, Streeten EA, Sorkin JD, Kuznetsova N, Shapses SA, Carleton SM, Shuldiner AR, Marini JC, Phillips CL, Goldstein SA, Leikin S, McBride DJ Jr: Variable bone fragility associated with an Amish COL1A2 variant and a knock-in mouse model. / J Bone Miner Res 2010,25(2):247-61. CrossRef
  24. Hanagata N, Li X, Morita H, Takemura T, Li J, Minowa T: Characterization of the osteoblast-specific transmembrane protein IFITM5 and analysis of IFITM5-deficient mice. / J Bone Miner Metab 2011,29(3):279-90. CrossRef
  25. Liu Y, Liu H, Titus L, Boden SD: Natural antisense transcripts enhance bone formation by increasing sense IFITM5 transcription. / Bone 2012,51(5):933-38. CrossRef
  26. The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2474/15/107/prepub
  
• 作者单位：Syndia Lazarus (1) (2) (3)
  Aideen M McInerney-Leo (1)
  Fiona A McKenzie (4) (5)
  Gareth Baynam (4) (5)
  Stephanie Broley (4)
  Barbra V Cavan (6)
  Craig F Munns (7) (8)
  Johannes Egbertus Hans Pruijs (9)
  David Sillence (10) (8)
  Paulien A Terhal (11)
  Karena Pryce (1)
  Matthew A Brown (1)
  Andreas Zankl (1) (2)
  Gethin Thomas (1)
  Emma L Duncan (1) (2) (3)
  
  1. Translational Research Institute, The University of Queensland Diamantina Institute, Woolloongabba, QLD, 4102, Australia
  2. UQ Centre for Clinical Research, University of Queensland, Herston, QLD, 4029, Australia
  3. Department of Endocrinology, Royal Brisbane & Women’s Hospital, Herston, QLD, 4029, Australia
  4. Genetic Services of Western Australia, Subiaco, WA, 6008, Australia
  5. School of Paediatrics and Child Health, The University of Western Australia, Crawley, WA, 6009, Australia
  6. Cebu Institute of Medicine, Cebu City, Cebu, 6000, Philippines
  7. Bone & Mineral Medicine, Endocrinology, The Children’s Hospital at Westmead, Westmead, NSW, 2145, Australia
  8. Connective Tissue Dysplasia Management Service The Sydney Children’s Hospital Network, Westmead, NSW, 2145, Australia
  9. Department of Orthopaedics, University Medical Centre Utrecht, 3584 EA, Utrecht, The Netherlands
  10. Discipline of Genetic Medicine, Sydney Children’s Hospital Clinical School, University of Sydney, Westmead, NSW, 2145, Australia
  11. Department of Medical Genetics, University Medical Centre Utrecht, 3508, Utrecht, The Netherlands
  
• ISSN：1471-2474

文摘

Background The genetic mutation resulting in osteogenesis imperfecta (OI) type V was recently characterised as a single point mutation (c.-14C-gt;?T) in the 5-untranslated region (UTR) of IFITM5, a gene encoding a transmembrane protein with expression restricted to skeletal tissue. This mutation creates an alternative start codon and has been shown in a eukaryotic cell line to result in a longer variant of IFITM5, but its expression has not previously been demonstrated in bone from a patient with OI type V. Methods Sanger sequencing of the IFITM5 5-UTR was performed in our cohort of subjects with a clinical diagnosis of OI type V. Clinical data was collated from referring clinicians. RNA was extracted from a bone sample from one patient and Sanger sequenced to determine expression of wild-type and mutant IFITM5. Results All nine subjects with OI type V were heterozygous for the c.-14C-gt;?T IFITM5 mutation. Clinically, there was heterogeneity in phenotype, particularly in the manifestation of bone fragility amongst subjects. Both wild-type and mutant IFITM5 mRNA transcripts were present in bone. Conclusions The c.-14C-gt;?T IFITM5 mutation does not result in an RNA-null allele but is expressed in bone. Individuals with identical mutations in IFITM5 have highly variable phenotypic expression, even within the same family.