Osteoporosis International

, Volume 25, Issue 2, pp 399–405

A brilliant breakthrough in OI type V

Review

Abstract

Interferon-induced transmembrane protein 5 or bone-restricted ifitm-like gene (Bril) was first identified as a bone gene in 2008, although no in vivo role was identified at that time. A role in human bone has now been demonstrated with a number of recent studies identifying a single point mutation in Bril as the causative mutation in osteogenesis imperfecta type V (OI type V). Such a discovery suggests a key role for Bril in skeletal regulation, and the completely novel nature of the gene raises the possibility of a new regulatory pathway in bone. Furthermore, the phenotype of OI type V has unique and quite divergent features compared with other forms of OI involving defects in collagen biology. Currently it appears that the underlying genetic defect in OI type V may be unrelated to collagen regulation, which also raises interesting questions about the classification of this form of OI. This review will discuss current knowledge of OI type V, the function of Bril, and the implications of this recent discovery.

Keywords

Bril Hyperplastic callus IFITM Interosseous membrane calcification Next generation sequencing Osteogenesis imperfecta 

References

  1. 1.
    Van Dijk FS, Pals G, Van Rijn RR, Nikkels PG, Cobben JM (2010) Classification of osteogenesis imperfecta revisited. European journal of medical genetics 53(1):1–5. doi:10.1016/j.ejmg.2009.10.007 PubMedCrossRefGoogle Scholar
  2. 2.
    Sykes B, Francis MJ, Smith R (1977) Altered relation of two collagen types in osteogenesis imperfecta. N Engl J Med 296(21):1200–1203. doi:10.1056/nejm197705262962104 PubMedCrossRefGoogle Scholar
  3. 3.
    Trelstad RL, Rubin D, Gross J (1977) Osteogenesis imperfecta congenita: evidence for a generalised molecular disorder of collagen. Lab Invest 36(5):501–508PubMedGoogle Scholar
  4. 4.
    Chu ML, Williams CJ, Pepe G, Hirsch JL, Prockop DJ, Ramirez F (1983) Internal deletion in a collagen gene in a perinatal lethal form of osteogenesis imperfecta. Nature 304(5921):78–80PubMedCrossRefGoogle Scholar
  5. 5.
    Steinmann B, Rao VH, Vogel A, Bruckner P, Gitzelmann R, Byers PH (1984) Cysteine in the triple-helical domain of one allelic product of the alpha 1(I) gene of type I collagen produces a lethal form of osteogenesis imperfecta. J Biol Chem 259(17):11129–11138PubMedGoogle Scholar
  6. 6.
    Cohn DH, Byers PH, Steinmann B, Gelinas RE (1986) Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro alpha 1(I) collagen allele. Proc Natl Acad Sci U S A 83(16):6045–6047PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Sykes B, Ogilvie D, Wordsworth P, Wallis G, Mathew C, Beighton P, Nicholls A, Pope FM, Thompson E, Tsipouras P et al (1990) Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COL1A1 and COL1A2. Am J Hum Genet 46(2):293–307PubMedCentralPubMedGoogle Scholar
  8. 8.
    Dalgleish R (1997) The human type I collagen mutation database. Nucleic Acids Res 25(1):181–187PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Dalgleish R (1998) The human collagen mutation database 1998. Nucleic Acids Res 26(1):253–255PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S, Hyland JC, Korkko J, Prockop DJ, De Paepe A, Coucke P, Symoens S, Glorieux FH, Roughley PJ, Lund AM, Kuurila-Svahn K, Hartikka H, Cohn DH, Krakow D, Mottes M, Schwarze U, Chen D, Yang K, Kuslich C, Troendle J, Dalgleish R, Byers PH (2007) Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat 28(3):209–221. doi:10.1002/humu.20429 PubMedCrossRefGoogle Scholar
  11. 11.
    Pihlajaniemi T, Dickson LA, Pope FM, Korhonen VR, Nicholls A, Prockop DJ, Myers JC (1984) Osteogenesis imperfecta: cloning of a pro-alpha 2(I) collagen gene with a frameshift mutation. J Biol Chem 259(21):12941–12944PubMedGoogle Scholar
  12. 12.
    Morello R, Bertin TK, Chen Y, Hicks J, Tonachini L, Monticone M, Castagnola P, Rauch F, Glorieux FH, Vranka J, Bachinger HP, Pace JM, Schwarze U, Byers PH, Weis M, Fernandes RJ, Eyre DR, Yao Z, Boyce BF, Lee B (2006) CRTAP is required for prolyl 3-hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell 127(2):291–304. doi:10.1016/j.cell.2006.08.039 PubMedCrossRefGoogle Scholar
  13. 13.
    Cabral WA, Barnes AM, Adeyemo A, Cushing K, Chitayat D, Porter FD, Panny SR, Gulamali-Majid F, Tishkoff SA, Rebbeck TR, Gueye SM, Bailey-Wilson JE, Brody LC, Rotimi CN, Marini JC (2012) A founder mutation in LEPRE1 carried by 1.5 % of West Africans and 0.4 % of African Americans causes lethal recessive osteogenesis imperfecta. Genetics in medicine: official journal of the American College of Medical Genetics 14(5):543–551. doi:10.1038/gim.2011.44 CrossRefGoogle Scholar
  14. 14.
    van Dijk FS, Nesbitt IM, Zwikstra EH, Nikkels PG, Piersma SR, Fratantoni SA, Jimenez CR, Huizer M, Morsman AC, Cobben JM, van Roij MH, Elting MW, Verbeke JI, Wijnaendts LC, Shaw NJ, Hogler W, McKeown C, Sistermans EA, Dalton A, Meijers-Heijboer H, Pals G (2009) PPIB mutations cause severe osteogenesis imperfecta. Am J Hum Genet 85(4):521–527. doi:10.1016/j.ajhg.2009.09.001 PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Christiansen HE, Schwarze U, Pyott SM, AlSwaid A, Al Balwi M, Alrasheed S, Pepin MG, Weis MA, Eyre DR, Byers PH (2010) Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta. Am J Hum Genet 86(3):389–398. doi:10.1016/j.ajhg.2010.01.034 PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Alanay Y, Avaygan H, Camacho N, Utine GE, Boduroglu K, Aktas D, Alikasifoglu M, Tuncbilek E, Orhan D, Bakar FT, Zabel B, Superti-Furga A, Bruckner-Tuderman L, Curry CJ, Pyott S, Byers PH, Eyre DR, Baldridge D, Lee B, Merrill AE, Davis EC, Cohn DH, Akarsu N, Krakow D (2010) Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet 86(4):551–559. doi:10.1016/j.ajhg.2010.02.022 PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Homan EP, Rauch F, Grafe I, Lietman C, Doll JA, Dawson B, Bertin T, Napierala D, Morello R, Gibbs R, White L, Miki R, Cohn DH, Crawford S, Travers R, Glorieux FH, Lee B (2011) Mutations in SERPINF1 cause osteogenesis imperfecta type VI. J Bone Miner Res 26(12):2798–2803. doi:10.1002/jbmr.487 PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Becker J, Semler O, Gilissen C, Li Y, Bolz HJ, Giunta C, Bergmann C, Rohrbach M, Koerber F, Zimmermann K, de Vries P, Wirth B, Schoenau E, Wollnik B, Veltman JA, Hoischen A, Netzer C (2011) Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta. Am J Hum Genet 88(3):362–371. doi:10.1016/j.ajhg.2011.01.015 PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Martínez-Glez V, Valencia M, Caparrós-Martín JA, Aglan M, Temtamy S, Tenorio J, Pulido V, Lindert U, Rohrbach M, Eyre D, Giunta C, Lapunzina P, Ruiz-Perez VL (2012) Identification of a mutation causing deficient BMP1/mTLD proteolytic activity in autosomal recessive osteogenesis imperfecta. Hum Mutat 33(2):343–350. doi:10.1002/humu.21647 PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Lapunzina P, Aglan M, Temtamy S, Caparros-Martin JA, Valencia M, Leton R, Martinez-Glez V, Elhossini R, Amr K, Vilaboa N, Ruiz-Perez VL (2010) Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta. Am J Hum Genet 87(1):110–114. doi:10.1016/j.ajhg.2010.05.016 PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Keupp K, Beleggia F, Kayserili H, Barnes Aileen M, Steiner M, Semler O, Fischer B, Yigit G, Janda Claudia Y, Becker J, Breer S, Altunoglu U, Grünhagen J, Krawitz P, Hecht J, Schinke T, Makareeva E, Lausch E, Cankaya T, Caparrós-Martín José A, Lapunzina P, Temtamy S, Aglan M, Zabel B, Eysel P, Koerber F, Leikin S, Garcia KC, Netzer C, Schönau E, Ruiz-Perez Victor L, Mundlos S, Amling M, Kornak U, Marini J, Wollnik B (2013) Mutations in WNT1 Cause Different Forms of Bone Fragility. The American Journal of Human Genetics In PressGoogle Scholar
  22. 22.
    Laine CM, Joeng KS, Campeau PM, Kiviranta R, Tarkkonen K, Grover M, Lu JT, Pekkinen M, Wessman M, Heino TJ, Nieminen-Pihala V, Aronen M, Laine T, Kröger H, Cole WG, Lehesjoki A-E, Nevarez L, Krakow D, Curry CJR, Cohn DH, Gibbs RA, Lee BH, Mäkitie O (2013) WNT1 Mutations in Early-Onset Osteoporosis and Osteogenesis Imperfecta. N Engl J Med 368 (19):1809–1816. doi:doi:10.1056/NEJMoa1215458 Google Scholar
  23. 23.
    Forlino A, Cabral WA, Barnes AM, Marini JC (2011) New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol 7(9):540–557PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    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 (2012) A single recurrent mutation in the 5'-UTR of IFITM5 causes osteogenesis imperfecta Type V. Am J Hum Genet 91(2):343–348. doi:10.1016/j.ajhg.2012.06.005 PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Farber C, Reich A, Barnes A, Cabral W, Riddle R, Digirolamo D, Clemens T, Marini J (2012) A Dominant Mutation of IFITM5 in Severe Osteogenesis Imperfecta Implicates an Interaction between Bril and PEDF in Bone. J Bone Miner Res 27 (Suppl 1):#1220Google Scholar
  26. 26.
    Moffatt P, Gaumond MH, Salois P, Sellin K, Bessette MC, Godin E, de Oliveira PT, Atkins GJ, Nanci A, Thomas G (2008) Bril: a novel bone-specific modulator of mineralization. J Bone Miner Res 23(9):1497–1508. doi:10.1359/jbmr.080412 PubMedCrossRefGoogle Scholar
  27. 27.
    Glorieux FH, Rauch F, Plotkin H, Ward L, Travers R, Roughley P, Lalic L, Glorieux DF, Fassier F, Bishop NJ (2000) Type V osteogenesis imperfecta: a new form of brittle bone disease. J Bone Miner Res 15(9):1650–1658. doi:10.1359/jbmr.2000.15.9.1650 PubMedCrossRefGoogle Scholar
  28. 28.
    Rauch F, Moffatt P, Cheung M, Roughley P, Lalic L, Lund AM, Ramirez N, Fahiminiya S, Majewski J, Glorieux FH (2013) Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.-14C > T mutation in all patients. J Med Genet 50(1):21–24. doi:10.1136/jmedgenet-2012-101307 PubMedCrossRefGoogle Scholar
  29. 29.
    Shapiro JR, Lietman C, Grover M, Lu JT, Nagamani SCS, Dawson BC, Baldridge DM, Bainbridge MN, Cohn DH, Blazo M, Roberts TT, Brennen F-S, Wu Y, Gibbs RA, Melvin P, Campeau PM, Lee BH (2013) Phenotypic variability of osteogenesis imperfecta type V caused by an IFITM5 mutation. J Bone Miner Res In Press. doi:10.1002/jbmr.1891
  30. 30.
    Semler O, Garbes L, Keupp K, Swan D, Zimmermann K, Becker J, Iden S, Wirth B, Eysel P, Koerber F, Schoenau E, Bohlander Stefan K, Wollnik B, Netzer C (2012) 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 91(2):349–357. doi:10.1016/j.ajhg.2012.06.011 PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Cheung MS, Glorieux FH, Rauch F (2007) Natural history of hyperplastic callus formation in osteogenesis imperfecta type V. J Bone Miner Res 22(8):1181–1186. doi:10.1359/jbmr.070418 PubMedCrossRefGoogle Scholar
  32. 32.
    Zeitlin L, Rauch F, Travers R, Munns C, Glorieux FH (2006) The effect of cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta type V. Bone 38(1):13–20. doi:10.1016/j.bone.2005.07.020 PubMedCrossRefGoogle Scholar
  33. 33.
    Arundel P, Offiah A, Bishop NJ (2011) Evolution of the radiographic appearance of the metaphyses over the first year of life in type V osteogenesis imperfecta: clues to pathogenesis. J Bone Miner Res 26(4):894–898. doi:10.1002/jbmr.258 PubMedCrossRefGoogle Scholar
  34. 34.
    Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E, Adams DJ, Xavier RJ, Farzan M, Elledge SJ (2009) The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile Virus, and dengue Virus. Cell 139(7):1243–1254PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, Chin CR, Feeley EM, Sims JS, Adams DJ, Wise HM, Kane L, Goulding D, Digard P, Anttila V, Baillie JK, Walsh TS, Hume DA, Palotie A, Xue Y, Colonna V, Tyler-Smith C, Dunning J, Gordon SB, Smyth RL, Openshaw PJ, Dougan G, Brass AL, Kellam P (2012) IFITM3 restricts the morbidity and mortality associated with influenza. Nature 484(7395):519–523PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Bailey CC, Huang IC, Kam C, Farzan M (2012) Ifitm3 limits the severity of acute influenza in mice. PLoS Pathog 8(9):e1002909. doi:10.1371/journal.ppat.1002909 PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Huang IC, Bailey CC, Weyer JL, Radoshitzky SR, Becker MM, Chiang JJ, Brass AL, Ahmed AA, Chi X, Dong L, Longobardi LE, Boltz D, Kuhn JH, Elledge SJ, Bavari S, Denison MR, Choe H, Farzan M (2011) Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus and influenza A Virus. PLoS Pathog 7(1):e1001258PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Hickford D, Frankenberg S, Shaw G, Renfree M (2012) Evolution of vertebrate interferon inducible transmembrane proteins. BMC Genomics 13(1):155PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Moffatt P, Salois P, Gaumond MH, St-Amant N, Godin E, Lanctot C (2002) Engineered viruses to select genes encoding secreted and membrane-bound proteins in mammalian cells. Nucleic Acids Res 30(19):4285–4294PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Hanagata N, Li X (2011) Osteoblast-enriched membrane protein IFITM5 regulates the association of CD9 with an FKBP11–CD81–FPRP complex and stimulates expression of interferon-induced genes. Biochem Biophys Res Commun 409(3):378–384. doi:10.1016/j.bbrc.2011.04.136 PubMedCrossRefGoogle Scholar
  41. 41.
    Hanagata N, Takemura T, Monkawa A, Ikoma T, Tanaka J (2007) Phenotype and gene expression pattern of osteoblast-like cells cultured on polystyrene and hydroxyapatite with pre-adsorbed type-I collagen. Journal of Biomedical Materials Research Part A I83(2):362–371CrossRefGoogle Scholar
  42. 42.
    Liu Y, Liu H, Titus L, Boden SD (2012) Natural antisense transcripts enhance bone formation by increasing sense IFITM5 transcription. Bone 51(5):933–938. doi:10.1016/j.bone.2012.07.024 PubMedCrossRefGoogle Scholar
  43. 43.
    Martin TJ, Allan EH, Ho PWM, Gooi JH, Quinn JMW, Gillespie MT, Krasnoperov V, Sims NA (2010) Communication Between EphrinB2 and EphB4 Within the Osteoblast Lineage. In: Choi Y (ed) Osteoimmunology - Interactions of the Immune and skeletal systems II vol 658. Advances in Experimental Medicine and Biology. Springer US, pp 51–60Google Scholar
  44. 44.
    Hanagata N, Li X, Morita H, Takemura T, Li J, Minowa T (2011) Characterization of the osteoblast-specific transmembrane protein IFITM5 and analysis of IFITM5-deficient mice. J Bone Miner Metab 29(3):279–290. doi:10.1007/s00774-010-0221-0 PubMedCrossRefGoogle Scholar
  45. 45.
    Lange UC, Adams DJ, Lee C, Barton S, Schneider R, Bradley A, Surani MA (2008) Normal germ line establishment in mice carrying a deletion of the Ifitm/Fragilis Gene family cluster. Mol Cell Biol 28(15):4688–4696. doi:10.1128/mcb.00272-08 PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Jia R, Pan Q, Ding S, Rong L, Liu SL, Geng Y, Qiao W, Liang C (2012) The N-terminal region of IFITM3 modulates its antiviral activity through regulating IFITM3 cellular localization. Journal of virology In Press. doi:10.1128/jvi.01828-12
  47. 47.
    Bogan R, Riddle RC, Li Z, Kumar S, Nandal A, Faugere M-C, Boskey A, Crawford SE, Clemens TL (2013) A mouse model for human osteogenesis imperfecta type VI. J Bone Miner Res In Press. doi:10.1002/jbmr.1892
  48. 48.
    Kasaai B, Gaumond M-H, Moffatt P (2013) Regulation of the Bone-restricted ifitm-like (Bril) gene transcription by Sp and Gli family members and CpG methylation. J Biol Chem In Press. doi:10.1074/jbc.M113.457010
  49. 49.
    Zankl A, Duncan Emma L, Leo Paul J, Clark Graeme R, Glazov Evgeny A, Addor M-C, Herlin T, Kim Chong A, Leheup Bruno P, McGill J, McTaggart S, Mittas S, Mitchell Anna L, Mortier Geert R, Robertson Stephen P, Schroeder M, Terhal P, Brown Matthew A (2012) Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB. Am J Hum Genet 90(3):494–501. doi:10.1016/j.ajhg.2012.01.003 PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Glazov EA, Zankl A, Donskoi M, Kenna TJ, Thomas GP, Clark GR, Duncan EL, Brown MA (2011) Whole-exome re-sequencing in a family quartet identifies < italic > POP1</italic > mutations as the cause of a novel skeletal dysplasia. PLoS Genet 7(3):e1002027PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Lacey DL, Boyle WJ, Simonet WS, Kostenuik PJ, Dougall WC, Sullivan JK, Martin JS, Dansey R (2012) Bench to bedside: elucidation of the OPG–RANK–RANKL pathway and the development of denosumab. Nat Rev Drug Discov 11(5):401–419PubMedCrossRefGoogle Scholar
  52. 52.
    Baron R, Rawadi G (2007) Targeting the Wnt/{beta}-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 148(6):2635–2643PubMedCrossRefGoogle Scholar
  53. 53.
    Moester MJ, Papapoulos SE, Lowik CW, van Bezooijen RL (2010) Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 87(2):99–107. doi:10.1007/s00223-010-9372-1 PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    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 (2011) Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A 155A(5):943–968. doi:10.1002/ajmg.a.33909 PubMedCrossRefGoogle Scholar
  55. 55.
    Crockett JC, Mellis DJ, Scott DI, Helfrich MH (2011) New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis. Osteoporos Int 22(1):1–20. doi:10.1007/s00198-010-1272-8 PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2013

Authors and Affiliations

  1. 1.University of Queensland Diamantina InstituteWoolloongabbaAustralia
  2. 2.Department of Endocrinology, Royal Brisbane and Women’s HospitalHerstonAustralia
  3. 3.University of Queensland Centre for Clinical ResearchHerstonAustralia
  4. 4.Shriners Hospital for ChildrenMontrealCanada

Personalised recommendations