Clinical characteristics and the identification of novel mutations of COL1A1 and COL1A2 in 61 Chinese patients with osteogenesis imperfecta

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by brittle bone fractures. The aim of the present study was to investigate the pathogenic gene mutation spectrum and clinical manifestations of mutations in collagen type I, alpha 1 (COL1A1) and collagen type I, alpha 2 (COL1A2) genes in Chinese patients with OI. A total of 61 unrelated Chinese OI patients with COL1A1 and COL1A2 mutations were recruited. All the exons and the exon-intron boundaries of the COL1A1 and COL1A2 genes were amplified and directly sequenced and lumbar spine bone mineral density was measured by dual‑energy X‑ray absorptiometry. The mutations of the 61 probands included 33 missense mutations, 8 nonsense mutations, 7 splicing variants and 13 frameshift mutations in COL1A1 and COL1A2 genes. A total of 25 novel mutations were identified, including 18 in COL1A1 and 7 in COL1A2. The mutations p.Gly257Arg, p.Gly767Ser and p.Gly821Ser in COL1A1 and p.Gly337Ser in COL1A2 may be located at a mutation hotspot for human OI due to the high repetition rate in OI patients. Family history was positive for OI in 33 probands (54%). All probands had suffered fractures and the most common fracture site was the femur. A total of 49 probands presented with blue sclerae (80.3%), 20 probands suffered from dentinogenesis imperfecta (32.8%) and 1 patient had hearing loss (1.6%). These findings may improve understanding of the pathogenic gene mutation spectrum and the clinical manifestations of mutations of COL1A1 and COL1A2 genes in Chinese patients with OI.