| Dr. Frederick Kaplan |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||
2009 Conference abstract
Osteochondromas & the FOP Metamorphogene
Kaplan FS, Deirmengian GK, Chakkalakal S, Shore EM
From the Departments of Orthopaedic Surgery, Medicine and Genetics, and the Center for Research in FOP & Related Disorders,
The University of Pennsylvania School of Medicine, Philadelphia, PA 19104.
e-mail: Frederick.Kaplan@uphs.upenn.edu
Sudden developmental novelty in highly conserved tissue repair mechanisms can lead to catastrophic medical consequences. A
recurrent missense mutation in the gene encoding activin receptor A type I/Activin-like kinase 2 (ACVR1/ALK2), a bone
morphogenetic protein type I receptor, creates a novel metamorphogene (ACVR1 c.617G>A;R206H) that causes fibrodysplasia
ossificans progressiva (FOP) (1,2). FOP is a rare and disabling autosomal dominant disorder that causes a plethora of pathologic
processes including dysregulated morphogenesis, abnormal tissue repair, skeletal metamorphosis, degenerative joint disease,
and osteochondromas (3).
Among the least explored functions of the FOP metamorphogene is its ability to stimulate osteochondromas. Osteochondromas
are associated with dysregulated BMP signaling and have been considered an atypical feature of FOP, but they may be under-
diagnosed because of their often asymptomatic nature (4). A recent study showed that ninety per cent of all FOP patients had
osteochondromas of the proximal tibia, and nearly one hundred per cent of all classically affected FOP patients had one or more
asymptomatic osteochondromas at other sites (5). Emerging animal models of FOP also confirm these findings (6).
Osteochondromas are thus a common phenotypic feature of FOP, a finding that expands the recognized consequences of the
FOP metamorphogene to include not only skeletal malformations and skeletal metamorphosis, but also benign osteochondral
neoplasms. The FOP metamorphogene dysregulates a highly conserved signaling pathway that has important implications for
developmental and regenerative medicine (7).
1. Shore EM et al. Nature Genetics 38: 525-527, 2006
2. Kaplan FS et al. Ann NY Acad Sci 1116: 113-133, 2007
3. Kaplan FS et al. Human Mutation 30: 379-390, 2009
4. O’Connell MP et al. J Cellular Biochem 102:1493-1503, 2007
5. Deirmengian GK et al. J Bone Joint Surg Am 90: 366-374, 2008
6. Chakkalakal SA et al. J Bone Min Res 23: s57 (1203), 2008
7. Shen Q et al. J Clin Invest October 12, 2009 (online)
Osteochondromas & the FOP Metamorphogene
Kaplan FS, Deirmengian GK, Chakkalakal S, Shore EM
From the Departments of Orthopaedic Surgery, Medicine and Genetics, and the Center for Research in FOP & Related Disorders,
The University of Pennsylvania School of Medicine, Philadelphia, PA 19104.
e-mail: Frederick.Kaplan@uphs.upenn.edu
Sudden developmental novelty in highly conserved tissue repair mechanisms can lead to catastrophic medical consequences. A
recurrent missense mutation in the gene encoding activin receptor A type I/Activin-like kinase 2 (ACVR1/ALK2), a bone
morphogenetic protein type I receptor, creates a novel metamorphogene (ACVR1 c.617G>A;R206H) that causes fibrodysplasia
ossificans progressiva (FOP) (1,2). FOP is a rare and disabling autosomal dominant disorder that causes a plethora of pathologic
processes including dysregulated morphogenesis, abnormal tissue repair, skeletal metamorphosis, degenerative joint disease,
and osteochondromas (3).
Among the least explored functions of the FOP metamorphogene is its ability to stimulate osteochondromas. Osteochondromas
are associated with dysregulated BMP signaling and have been considered an atypical feature of FOP, but they may be under-
diagnosed because of their often asymptomatic nature (4). A recent study showed that ninety per cent of all FOP patients had
osteochondromas of the proximal tibia, and nearly one hundred per cent of all classically affected FOP patients had one or more
asymptomatic osteochondromas at other sites (5). Emerging animal models of FOP also confirm these findings (6).
Osteochondromas are thus a common phenotypic feature of FOP, a finding that expands the recognized consequences of the
FOP metamorphogene to include not only skeletal malformations and skeletal metamorphosis, but also benign osteochondral
neoplasms. The FOP metamorphogene dysregulates a highly conserved signaling pathway that has important implications for
developmental and regenerative medicine (7).
1. Shore EM et al. Nature Genetics 38: 525-527, 2006
2. Kaplan FS et al. Ann NY Acad Sci 1116: 113-133, 2007
3. Kaplan FS et al. Human Mutation 30: 379-390, 2009
4. O’Connell MP et al. J Cellular Biochem 102:1493-1503, 2007
5. Deirmengian GK et al. J Bone Joint Surg Am 90: 366-374, 2008
6. Chakkalakal SA et al. J Bone Min Res 23: s57 (1203), 2008
7. Shen Q et al. J Clin Invest October 12, 2009 (online)
The MHE Research Foundation, we comply with the HONcode standard for health trust worthy information: By the Health On the Net Foundation. Click
here to verify.# HON Conduct 282463 and is linked on the NIH National Library of Medicine, Directory of Health Organizations (SIS) website, as well as
the link for Patient Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life sciences a free
online service providing access to the very best Web resources for education and research located in the UK
here to verify.# HON Conduct 282463 and is linked on the NIH National Library of Medicine, Directory of Health Organizations (SIS) website, as well as
the link for Patient Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life sciences a free
online service providing access to the very best Web resources for education and research located in the UK
The MHE Research Foundation is proud to be working with the EuroBoNeT consortium, a European Commission granted Network of Excellence for
studying the pathology and genetics of bone tumors.
studying the pathology and genetics of bone tumors.
| This website is regularly reviewed by members of the Scientific and Medical Advisory Board of the MHE Research Foundation. All online submission forms use (SSL 3.0, RC4 with 128 bit encryption (High); RSA with 1024 bit exchange) Protocol with Privacy protection. Our goal is to make this website as safe and user friendly as possible. |
| The MHE Research Foundation is a participating member organization of the United States Bone and Joint Decade, (USBJD) & the USBJD Rare Bone Disease Patient Network |
| Email the webmaster: webmaster@mheresearchfoundation.org Materials on this website are protected by copyright Copyright © 2009 The MHE Research Foundation |
| This web page was updated last on 9/19/09, 4:0O pm Eastern time |
| Written consent must be obtained to attach web pages or the files attached to this website. Please email webmaster. |
Disclaimer: While many find the information useful, it is in no way a substitute for professional medical care.
The information provided here is for educational and informational purposes only. This website does not engage in the practice of medicine. In all cases we
recommend that you consult your own physician regarding any course of treatment or medicine.
The information provided here is for educational and informational purposes only. This website does not engage in the practice of medicine. In all cases we
recommend that you consult your own physician regarding any course of treatment or medicine.
The MHE Research Foundation is proud to be an affiliate of the Society For Glycobiology
| Photo's taken during the Third International MHE Research Conference |
