Genotypic and phenotypic characterization of Chinese patients with osteogenesis imperfecta

作者：Lulu Li, Bin Mao, Shan Li, Jifang Xiao, Han Wang, Jing Zhang, Xiuzhi Ren, Yanzhou Wang, Yiyang Wu, Yixuan Cao, Chaoxia Lu, Jingsong Gao, Yi You, Feiyue Zhao, Xingzhu Geng, Yaxiong Xiao, Chendan Jiang, Yuqian Ye, Tao Yang, Xiuli Zhao, Xue Zhang · 发表于：Human Mutation · 年份：2019 · DOI：10.1002/humu.23718 · 被引用次数：45 · 研究领域：Connective tissue disorders research、Bone and Dental Protein Studies

Osteogenesis imperfecta (OI) is a rare hereditary skeletal dysplasia, characterized by recurrent fractures and bone deformity. This study presents a clinical characterization and mutation analysis of 668 patients, aiming to establish the mutation spectrum and to elucidate genotype-phenotype correlations in Chinese OI patients. We identified 274 sequence variants (230 in type I collagen encoding genes and 44 in noncollagen genes), including 102 novel variants, in 340 probands with a detection rate of 90%. Compared with 47 loss-of-function variants detected in COL1A1, neither nonsense nor frameshift variants were found in COL1A2 (p < 0.0001). The major cause of autosomal recessive OI was biallelic variants in WNT1 (56%, 20/36). It is noteworthy that three genomic rearrangements, including one gross deletion and one gross duplication in COL1A1 as well as one gross deletion in FKBP10, were detected in this study. Of ten individuals with glycine substitutions that lie towards the N-terminal end of the triple-helical region of the α1(I) chain, none exhibited hearing loss, suggesting a potential genotype-phenotype correlation. The findings in this study expanded the mutation spectrum and identified novel correlations between genotype and phenotype in Chinese OI patients.