The phenotype and genotype of fibrodysplasia ossificans progressiva in China: a report of 72 cases.
Fibrodysplasia ossificans progressiva, an ultra-rare and disabling genetic disorder of skeletal malformations and progressive heterotopic ossification (HO), is the most catastrophic condition of skeletal metamorphosis in humans. We studied 72 patients with FOP in China and analyzed their phenotypes and genotypes comprising the world's largest ethnically homogeneous population of FOP patients. Ninety-nine percent of patients (71/72 cases) were of Han nationality; and 1% of patients (1/72 cases) were of Hui nationality. Based on clinical examination, 92% of patients (66/72 cases) had classic FOP; 4% of patients (3/72 cases) were FOP-plus; and 4% of patients (3/72) were FOP variants. Importantly, all individuals with FOP had mutations in the protein-coding region of activin A receptor, type I/activin-like kinase 2 (ACVR1/ALK2). Ninety-seven percent of FOP patients (70/72 cases) had the canonical c.617G>A (p.R206H) mutation, while 3% of FOP patients (2/72 cases) had variant mutations in ACVR1/ALK2. Taken together, the genotypes and phenotypes of individuals with FOP from the Han nationality in China are similar to those reported elsewhere and support the fidelity of this ultra-rare disorder in the world's most highly populated nation and across wide racial, ethnic, gender and geographic distributions.
Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Wei
W
Zhang
Keqin
K
Zhang
Lige
L
Song
Jing
J
Pang
Hongxing
H
Ma
Eileen M
EM
Shore
Frederick S
FS
Kaplan
Peijun
P
Wang
D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D002681:China / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009221:Myositis Ossificans / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D011859:Radiography; D011877:Radionuclide Imaging; D055815:Young Adult
ACVR1; ALK2; Bone morphogenetic protein; Fibrodysplasia ossificans progressiva; Heterotopic ossification