Zhang Hao, Yue Hua, Wang Chun, Hu Weiwei, Gu Jiemei, He Jinwei, Fu Wenzhen, Hu Yunqiu, Li Miao, Zhang Zhenlin
Department of Osteoporosis and Bone Diseases, Metabolic Bone Diseases and Genetic Research Unit, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
Mol Med Rep. 2016 Nov;14(5):4918-4926. doi: 10.3892/mmr.2016.5835. Epub 2016 Oct 12.
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.
成骨不全症（OI）是一种遗传性结缔组织疾病，其特征为脆性骨折。本研究的目的是调查中国成骨不全症患者中I型胶原蛋白α1（COL1A1）基因和I型胶原蛋白α2（COL1A2）基因的致病基因突变谱及突变的临床表现。共招募了61例携带COL1A1和COL1A2基因突变的非亲缘关系的中国成骨不全症患者。对COL1A1和COL1A2基因的所有外显子及外显子-内含子边界进行扩增并直接测序，采用双能X线吸收法测量腰椎骨密度。61例先证者的突变包括COL1A1和COL1A2基因中的33个错义突变、8个无义突变、7个剪接变异和13个移码突变。共鉴定出25个新突变，其中COL1A1基因有18个，COL1A2基因有7个。由于在成骨不全症患者中的重复率较高，COL1A1基因中的p.Gly257Arg、p.Gly767Ser和p.Gly821Ser突变以及COL1A2基因中的p.Gly337Ser突变可能位于人类成骨不全症的突变热点区域。33例先证者（54%）的成骨不全症家族史呈阳性。所有先证者均有骨折史，最常见的骨折部位是股骨。共有49例先证者出现蓝色巩膜（80.3%），20例先证者患有牙本质发育不全（32.8%），1例患者有听力损失（1.6%）。这些发现可能有助于提高对中国成骨不全症患者中COL1A1和COL1A2基因致病基因突变谱及突变临床表现的认识。
