Kaplan Frederick S, Groppe Jay C, Xu Meiqi, Towler O Will, Grunvald Eduardo, Kalunian Kenneth, Kallish Staci, Al Mukaddam Mona, Pignolo Robert J, Shore Eileen M
Department of Orthopaedic Surgery, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Medicine, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Am J Med Genet A. 2022 Mar;188(3):806-817. doi: 10.1002/ajmg.a.62585. Epub 2021 Dec 2.
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; ACVR1 ) responsible for a mild nonclassic fibrodysplasia ossificans progressiva (FOP) phenotype. Both families include people with the ultrarare ACVR1 variant who exhibit features of FOP while other individuals currently do not express any clinical signs of FOP. Thus, the mild ACVR1 variant greatly expands the scope and understanding of this rare disorder.
基因变异对于阐释临床表型、辅助体格诊断、指导遗传咨询、理解疾病的分子基础以及潜在地推动药物研发都至关重要。在此，我们描述了两个家系，其中存在一种极其罕见的激活素受体1（ACVR1）功能获得性致病变异（密码子375，精氨酸>脯氨酸；ACVR1），该变异导致了一种轻度的非典型进行性骨化性纤维发育不良（FOP）表型。两个家系中都有携带这种极其罕见的ACVR1变异的人，他们表现出FOP的特征，而其他个体目前未表现出FOP的任何临床症状。因此，这种轻度的ACVR1变异极大地扩展了对这种罕见疾病的认识范围。
