Abstract
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and presents progressive extra-skeletal ossification. The 617G>A (R206H) mutation in the activin receptor type IA (ACVR1) gene has been identified in all examined individuals with FOP of various ethnic groups, including Caucasian and Chinese descents. Here, we examined three Japanese patients with FOP for ACVR1 mutations. We identified the 617G>A mutation in all three patients. Our results suggest that the mutation in the ACVR1 gene is common and recurrent in the global population.
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Bellus GA, Hefferon TW, Ortiz de Luna RI, Hecht JT, Horton WA, Machado M, Kaitila I, McIntosh I, Francomano CA (1995) Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am J Hum Genet 56(2):368–373
Cohen RB, Hahn GV, Tabas JA, Peeper J, Levitz CL, Sando A, Sando N, Zasloff M, Kaplan FS (1993) The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J Bone Joint Surg Am 75(2):215–219
Ikegawa S, Fukushima Y, Isomura M, Takada F, Nakamura Y (1995) Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients. Hum Genet 96(3):309–311
Kaplan FS, McCluskey W, Hahn G, Tabas JA, Muenke M, Zasloff MA (1993) Genetic transmission of fibrodysplasia ossificans progressiva. Report of a family. J Bone Joint Surg Am 75(8):1214–1220
Kaplan FS, Shore EM, Connor JM (2002) Fibrodysplasia ossificans progressiva (FOP). In: Royce PM, Steinmann B (eds) Connective tissue and its heritable disorders: molecular, genetic, and medical aspects, 2nd edn. Wiley-Liss, New York, pp 827–840
Kaplan FS, Glaser DL, Hebela N, Shore EM (2004) Heterotopic ossification. J Am Acad Orthop Surg 12(2):116–125
Lin GT, Chang HW, Liu CS, Huang PJ, Wang HC, Cheng YM (2006) De novo 617G-A nucleotide mutation in the ACVR1 gene in a Taiwanese patient with fibrodysplasia ossificans progressiva. J Hum Genet 51(12):1083–1086
Nishimura G, Fukushima Y, Ohashi H, Ikegawa S (1995) Atypical radiological findings in achondroplasia with uncommon mutation of the fibroblast growth factor receptor-3 (FGFR-3) gene (Gly to Cys transition at codon 375). Am J Med Genet 59(3):393–395
Penrose LS (1955) Parental age and mutation. Lancet 269(6885):312–313
Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux P, Le Merrer M, Munnich A (1994) Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature 371(6494):252–254
Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, Winokur ST, Wasmuth JJ (1994) Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 78(2):335–342
Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Brown MA, Kaplan FS (2006) A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 38(5):525–527
Superti-Furga A, Eich G, Bucher HU, Wisser J, Giedion A, Gitzelmann R, Steinmann B (1995) A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia. Eur J Pediatr 154(3):215–219
Tuente W, Becker PE, Von Knorre GV (1967) Zur Genetik der Myositis ossificans progressiva. Humangenetik 4(4):320–351
Acknowledgments
We thank the patients and their relatives who co-operated in this study, and Ms. Tomoko Kusadokoro for her technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nakajima, M., Haga, N., Takikawa, K. et al. The ACVR1 617G>A mutation is also recurrent in three Japanese patients with fibrodysplasia ossificans progressiva. J Hum Genet 52, 473–475 (2007). https://doi.org/10.1007/s10038-007-0128-3
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1007/s10038-007-0128-3
Keywords
This article is cited by
-
The biological function of type I receptors of bone morphogenetic protein in bone
Bone Research (2016)
-
Phenotypic differences of patients with fibrodysplasia ossificans progressive due to p.Arg258Ser variants of ACVR1
Human Genome Variation (2015)
-
Fibrodysplasia ossificans progressiva
Medizinische Genetik (2012)
-
Deformity of the great toe in fibrodysplasia ossificans progressiva
Journal of Orthopaedic Science (2010)
-
Rarely occurring mutation of ACVR1 gene in Moroccan patient with fibrodysplasia ossificans progressiva
Clinical Rheumatology (2010)
