IFITM5 pathogenic variant causes osteogenesis imperfecta V with various phenotype severity in Ukrainian and Vietnamese patients
Tóm tắt
Osteogenesis imperfecta (OI) covers a spectrum of bone fragility disorders. OI is classified into five types; however, the genetic causes of OI might hide in pathogenic variants of 20 different genes. Often clinical OI types mimic each other. This sometimes makes it impossible to identify the OI type clinically, which can be a risk for patients. Up to 90% of OI types I–IV are caused by pathogenic variants in the COL1A1/2 genes. OI type V is caused by the c.-14C > T pathogenic variant in the 5′UTR of the IFITM5 gene and is characterized by hyperplastic callus formation and the ossification of interosseous membranes. In the current study, we performed IFITM5 5′UTR region mutational analysis using Sanger sequencing on 90 patients who were negative for COL1A1/2 pathogenic variants. We also investigated the phenotypes of five patients with genetically confirmed OI type V. The proportion of OI type V patients in our cohort of all OI patients was 1.48%. In one family, there was a history of OI in at least three generations. Phenotype severity differed from mild to extremely severe among patients, but all patients harbored the same typical pathogenic variant. One patient had no visible symptoms of OI type V and was suspected to have had OI type IV previously. We also identified a case of extremely severe hyperplastic callus in a 15-year-old male, who has hearing loss and brittleness of teeth. OI type V is underlined with some unique clinical features; however, not all patients develop them. The phenotype spectrum might be even broader than previously suspected, including typical OI features: teeth brittleness, bluish sclera, hearing loss, long bones deformities, and joint laxity. We suggest that all patients negative for COL1A1/2 pathogenic variants be tested for the presence of an IFITM5 pathogenic variant, even if they are not expressing typical OI type V symptoms. Further studies on the pathological nature and hyperplastic callus formation mechanisms of OI type V are necessary.
Tài liệu tham khảo
Byers PH, Steiner RD. Osteogenesis imperfecta. Annu Rev Med. 1992;43:269–82.
Van Dijk FS, Pals G, Van Rijn RR, Nikkels PGJ, Cobben JM. Classification of Osteogenesis Imperfecta revisited. Eur J Med Genet. 2010;53:1–5.
Rauch F, Glorieux F. Osteogenesis imperfecta. Lancet. 2004;363(9418):1377–85.
Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16:101–16.
Fratzl-Zelman N, Misof BM, Roschger P, Klaushofer K. Classification of osteogenesis imperfecta. Wien Med Wochenschr. 2015;165:264–70.
Van Dijk FS, Sillence DO. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 2014;164A:1470–81.
Marini JC, Forlino A, Bächinger HP, Bishop NJ, Byers PH, De PA, et al. Osteogenesis imperfecta. Nat Rev Dis Primers. 2017;3:17052 Nature Publishing Group.
Shapiro JR. Clinical and genetic classification of osteogenesis imperfecta and epidemiology. In: Osteogenes. Imperfecta: A Translational Approach to Brittle Bone disease. Elsevier Inc (London, Waltham, San Diego); 2013. p. 15–22.
Lange UC, Saitou M, Western PS, Barton SC, Surani MA. The fragilis interferon-inducible gene family of transmembrane proteins is associated with germ cell specification in mice. BMC Dev Biol. 2003;3:1.
Bardai G, Moffatt P, Glorieux FH, Rauch F. DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum. Osteoporos Int. 2016;27:3607–13.
Osteogenesis Imperfecta Variant Database - Leiden Open Variation Database [Internet]. https://oi.gene.le.ac.uk/. Accessed 17 Dec 2018.
Baldridge D, Schwarze U, Morello R, Lennington J, Bertin TK, Pace JM, et al. CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Hum Mutat. 2008;29:1435–42.
van Dijk FS, Nesbitt IM, Zwikstra EH, Nikkels PGJ, Piersma SR, Fratantoni SA, et al. PPIB mutations cause severe osteogenesis imperfecta. Am J Hum Genet. 2009;85:521–7.
Shaheen R, Al-Owain M, Sakati N, Alzayed ZS, Alkuraya FS. FKBP10 and Bruck syndrome: phenotypic heterogeneity or call for reclassification? Am J Hum Genet. 2010;87:306–7 author reply 308. Elsevier.
Valadares ER, Carneiro TB, Santos PM, Oliveira AC, Zabel B. What is new in genetics and osteogenesis imperfecta classification? J Pediatr. 2014;90:536–41.
van Dijk FS, Zillikens MC, Micha D, Riessland M, Marcelis CLM, de Die-Smulders CE, et al. PLS3 mutations in X-linked osteoporosis with fractures. N Engl J Med. 2013;369:1529–36.
Shaheen R, Alazami AM, Alshammari MJ, Faqeih E, Alhashmi N, Mousa N, et al. Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation. J Med Genet. 2012;49:630–5.
Garbes L, Kim K, Rieß A, Hoyer-Kuhn H, Beleggia F, Bevot A, et al. Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta. Am J Hum Genet. 2015;96:432–9 The American Society of Human Genetics.
Symoens S, Malfait F, D’hondt S, Callewaert B, Dheedene A, Steyaert W, et al. Deficiency for the ER-stress transducer OASIS causes severe recessive osteogenesis imperfecta in humans. Orphanet J Rare Dis. 2013;8:154.
Mendoza-Londono R, Fahiminiya S, Majewski J, Tétreault M, Nadaf J, Kannu P, et al. Recessive osteogenesis imperfecta caused by missense mutations in SPARC. Am J Hum Genet. 2015;96:979–85.
Pyott SM, Tran TT, Leistritz DF, Pepin MG, Mendelsohn NJ, Temme RT, et al. WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta. Am J Hum Genet The American Society of Human Genetics. 2013;92:590–7.
Becker J, Semler O, Gilissen C, Li Y, Bolz HJ, Giunta C, et al. Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2011;88:362–71.
Marini JC, Reich A, Smith SM. Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation. Curr Opin Pediatr. 2014;26:500–7.
Glorieux FH, Rauch F, Plotkin H, Ward L, Travers R, Roughley P, et al. Type V osteogenesis imperfecta: a new form of brittle bone disease. J Bone Miner Res [Internet] John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR). 2000;15:1650–8.
Rauch F, Moffatt P, Cheung M, Roughley P, Lalic L, Lund AM, et al. Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.−14C>T mutation in all patients. J Med Genet. 2013;50:21–4.
Cheung MS, Glorieux FH, Rauch F. Natural history of hyperplastic callus formation in osteogenesis imperfecta type V. J Bone Miner Res. 2007;22:1181–6. A.
Balasubramanian M, Parker MJ, Dalton A, Giunta C, Lindert U, Peres LC, et al. Genotype–phenotype study in type V osteogenesis imperfecta. Clin Dysmorphol. 2013;22:93–101.
Fitzgerald J, Holden P, Wright H, Wilmot B, Hata A, Steiner RD, et al. Phenotypic variability in individuals with type v osteogenesis imperfecta with identical ifitm5 mutations. J Rare Disord. 2013;1:37–42.
Guillén-Navarro E, Ballesta-Martínez MJ, Valencia M, Bueno AM, Martinez-Glez V, López-González V, et al. Two mutations in IFITM5 causing distinct forms of osteogenesis imperfecta. Am J Med Genet A. 2014;164:1136–42.
Shapiro JR, Lietman C, Grover M, Lu JT, Nagamani SC, Dawson BC, et al. Phenotypic variability of osteogenesis imperfecta type V caused by an IFITM5 mutation. J Bone Miner Res [Internet] Wiley-Blackwell. 2013;28:1523–30.
Grover M, Campeau PM, Lietman CD, Lu JT, Gibbs RA, Schlesinger AE, et al. Osteogenesis imperfecta without features of type V caused by a mutation in the IFITM 5 gene. J Bone Miner Res. 2013;28:2333–7.
Cho T-J, Lee K-E, Lee S-K, Song SJ, Kim KJ, Jeon D, et al. A single recurrent mutation in the 5′-UTR of IFITM5 causes osteogenesis imperfecta type V. Am J Hum Genet. 2012;91:343–8.
Semler O, Garbes L, Keupp K, Swan D, Zimmermann K, Becker J, et al. 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;91:349–57.
Lazarus S, McInerney-Leo AM, McKenzie FA, Baynam G, Broley S, Cavan BV, et al. The IFITM5 mutation c.-14C > T results in an elongated transcript expressed in human bone; and causes varying phenotypic severity of osteogenesis imperfecta type V. BMC Musculoskelet Disord. 2014;15:107.
Lietman CD, Marom R, Munivez E, Bertin TK, Jiang M-M, Chen Y, et al. A transgenic mouse model of OI type V supports a neomorphic mechanism of the IFITM5 mutation. J Bone Miner Res Wiley-Blackwell. 2015;30:489–98.
Zhytnik L, Maasalu K, Reimann E, Prans E, Kõks S, Märtson A. Mutational analysis of COL1A1 and COL1A2 genes among Estonian osteogenesis imperfecta patients. Hum Genomics. 2017;11:19.
Ho Duy B, Zhytnik L, Maasalu K, Kändla I, Prans E, Reimann E, et al. Mutation analysis of the COL1A1 and COL1A2 genes in Vietnamese patients with osteogenesis imperfecta. Hum Genomics. 2016;10:27.
Binh HD, Maasalu K, Dung VC, Ngoc CTB, Hung TT, Nam TV, et al. The clinical features of osteogenesis imperfecta in Vietnam. Int Orthop. 2017;41:21–9.
Liu Y, Asan MD, Lv F, Xu X, Wang J, et al. Gene mutation spectrum and genotype-phenotype correlation in a cohort of Chinese osteogenesis imperfecta patients revealed by targeted next generation sequencing. Osteoporos Int. 2017;28:2985–95.
Essawi O, Symoens S, Fannana M, Darwish M, Farraj M, Willaert A, et al. Genetic analysis of osteogenesis imperfecta in the Palestinian population: molecular screening of 49 affected families. Mol Genet Genomic Med. 2018;6:15–26.
Zhang Z, Li M, He J-W, Fu W-Z, Zhang C-Q, Zhang Z-L. Phenotype and genotype analysis of Chinese patients with osteogenesis imperfecta type. PLoS One. 2013;8:e72337 V. Toft M, editor.
Hanagata N. IFITM5 mutations and osteogenesis imperfecta. J Bone Miner Metab. 2016;34:123–31.
Liu B-Y, Lu Y-Q, Han F, Wang Y, Mo X-K, Han J-X. Effects of the overexpression of IFITM5 and IFITM5 c.-14C>T mutation on human osteosarcoma cells. Oncol Lett. 2017;13:111–8.
Shapiro JR, Lietman C, Grover M, Lu JT, Nagamani SC, Dawson BC, et al. Phenotypic variability of osteogenesis imperfecta type V caused by an IFITM 5 mutation. J Bone Miner Res. 2013;28:1523–30.
Kim O-H, Jin D-K, Kosaki K, Kim J-W, Cho SY, Yoo WJ, et al. Osteogenesis imperfecta type V: clinical and radiographic manifestations in mutation confirmed patients. Am J Med Genet A. 2013;161:1972–9.
Reich A, Bae AS, Barnes AM, Cabral WA, Hinek A, Stimec J, et al. Type V OI primary osteoblasts display increased mineralization despite decreased COL1A1 expression. J Clin Endocrinol Metab. 2015;100:E325–32.