期刊
HUMAN MUTATION
卷 40, 期 5, 页码 588-600出版社
WILEY
DOI: 10.1002/humu.23718
关键词
Chinese cohort; genomic rearrangements; genotype-phenotype correlations; mutation spectrum; osteogenesis imperfecta
资金
- National Key Research and Development Program of China [2016YFE0128400, 2016YFC0905100]
- National Natural Science Foundation of China [81472053, 81871749]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-3-003]
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.
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