TY - JOUR
T1 - An ACVR1R375P pathogenic variant in two families with mild fibrodysplasia ossificans progressiva
AU - Kaplan, Frederick S.
AU - Groppe, Jay C.
AU - Xu, Meiqi
AU - Towler, O. Will
AU - Grunvald, Eduardo
AU - Kalunian, Kenneth
AU - Kallish, Staci
AU - Al Mukaddam, Mona
AU - Pignolo, Robert J.
AU - Shore, Eileen M.
N1 - Funding Information:
This work was supported in part by the International Fibrodysplasia Ossificans Progressiva Association (IFOPA), the Center for Research in FOP and Related Disorders, the Ian Cali Endowment for FOP Research, the Whitney Weldon Endowment for FOP Research, The Ashley Martucci FOP Research Fund, The Isaac and Rose Nassau Professorship of Orthopedic Molecular Medicine (to F.S.K.), the Cali‐Weldon Professorship of FOP Research (to E.M.S.), the Ian Cali Distinguished Clinician–Scientist (to M.A.M.), the Robert and Arlene Kogod Professorship in Geriatric Medicine at the Mayo Clinic (to R.J.P.) and the Penn Center for Musculoskeletal Disorders. The authors thank Mr. Robert Caron and Mrs. Kamlesh Rai for their invaluable technical and administrative assistance.
Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2022/3
Y1 - 2022/3
N2 - Genetic variants are vital in informing clinical phenotypes, aiding physical diagnosis, guiding genetic counseling, understanding the molecular basis of disease, and potentially stimulating drug development. Here we describe two families with an ultrarare ACVR1 gain-of-function pathogenic variant (codon 375, Arginine > Proline; ACVR1R375P) responsible for a mild nonclassic fibrodysplasia ossificans progressiva (FOP) phenotype. Both families include people with the ultrarare ACVR1R375P variant who exhibit features of FOP while other individuals currently do not express any clinical signs of FOP. Thus, the mild ACVR1R375P variant greatly expands the scope and understanding of this rare disorder.
AB - Genetic variants are vital in informing clinical phenotypes, aiding physical diagnosis, guiding genetic counseling, understanding the molecular basis of disease, and potentially stimulating drug development. Here we describe two families with an ultrarare ACVR1 gain-of-function pathogenic variant (codon 375, Arginine > Proline; ACVR1R375P) responsible for a mild nonclassic fibrodysplasia ossificans progressiva (FOP) phenotype. Both families include people with the ultrarare ACVR1R375P variant who exhibit features of FOP while other individuals currently do not express any clinical signs of FOP. Thus, the mild ACVR1R375P variant greatly expands the scope and understanding of this rare disorder.
KW - ACVR1
KW - activin receptor-like kinase 2 (ALK2)
KW - bone morphogenetic protein signaling
KW - fibrodysplasia ossificans progressiva (FOP)
KW - heterotopic ossification
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U2 - 10.1002/ajmg.a.62585
DO - 10.1002/ajmg.a.62585
M3 - Article
C2 - 34854557
AN - SCOPUS:85120437681
VL - 188
SP - 806
EP - 817
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 3
ER -