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. 2022 Mar;188(3):806-817.
doi: 10.1002/ajmg.a.62585. Epub 2021 Dec 2.

An ACVR1R375P pathogenic variant in two families with mild fibrodysplasia ossificans progressiva

Frederick S Kaplan  1   2   3 , Jay C Groppe  4 , Meiqi Xu  1   3 , O Will Towler  1   3 , Eduardo Grunvald  5 , Kenneth Kalunian  6 , Staci Kallish  3   7 , Mona Al Mukaddam  1   2   3 , Robert J Pignolo  8 , Eileen M Shore  1   3   9
Affiliations

An ACVR1R375P pathogenic variant in two families with mild fibrodysplasia ossificans progressiva

Frederick S Kaplan et al. Am J Med Genet A. 2022 Mar.

Abstract

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.

Keywords: ACVR1; activin receptor-like kinase 2 (ALK2); bone morphogenetic protein signaling; fibrodysplasia ossificans progressiva (FOP); heterotopic ossification.

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References

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