Genotypic and phenotypic characterization of Chinese patients with osteogenesis imperfecta
Genotypic and phenotypic characterization of Chinese patients with osteogenesis imperfecta
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中国成骨不全症患者的基因型和表型特征
DOI：
10.1002/humu.23718
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发表时间：
2019-05-01
期刊：
影响因子：
3.9
通讯作者：
Zhang, Xue
中科院分区：
文献类型：
--
作者：
Li, Lulu;Mao, Bin;Zhang, Xue
成骨不全症是一种罕见的遗传性骨骼发育不良，以复发性骨折和骨畸形为特征。本研究对668例患者的临床特征和突变进行了分析，旨在建立突变谱，阐明中国OI患者的基因型-表型相关性。我们在340个先证者中发现了274个序列变异（230个在I型胶原编码基因中，44个在非胶原基因中），包括102个新变异，检出率为90%。与COL1A1中检测到的47个功能缺失变异相比，COL1A2中既没有发现无意义变异，也没有发现移码变异（p < 0.0001）。常染色体隐性OI的主要原因是WNT1的双等位基因变异（56%,20/36）。值得注意的是，在本研究中发现了三个基因组重排，包括COL1A1的一个总缺失和一个总重复，以及FKBP10的一个总缺失。在alpha 1(I)链三螺旋区n端有甘氨酸取代的10个个体中，没有人表现出听力损失，这表明可能存在基因型-表型相关性。本研究的发现扩大了突变谱，并确定了中国OI患者基因型和表型之间的新相关性。
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 alpha 1(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.