目的 对COL1A2新发突变致1例新生儿成骨不全症的临床表型及基因变异特征进行分析,提高对成骨不全症(OI)的诊断和认识。方法 回顾福建中医药大学附属厦门市第三医院儿科2017年8月确诊的1例新生儿成骨不全症临床资料及辅助检查,并提取患儿及其父母外周血DNA,采用全序列外显子基因检测技术检测成骨不全症相关基因,对突变基因进一步分析并复习相关文献。结果 患儿的COL1A1基因未检出致病性变异,而COL1A2 基因检测发现一杂合错义突变(c.G2882A,p.G961D),PubMed及HGMD数据库均未见报道,该错义突变来自母亲,而其父正常。结论 依据本例患儿临床信息、疾病遗传模式和Exomiser软件综合评价,预测COL1A2 基因新发突变(c.G2882A,p.G961D)是成骨不全症致病突变。
Abstract
Objective To analyze and summarize the clinical phenotype and gene mutation characteristics of a de novo COL1A2 gene mutation in a newborn with osteogenesis imperfecta (OI),in order to improve the diagnosis and understanding of OI. Methods Clinical data and test results were reviewed from a newborn diagnosed with OI in the department of Pediatrics of the Third Hospital of Xiamen Affiliated Hospital in August 2017. In addition, the newborn and her parents′ peripheral blood genomic DNA were extracted, and the genes related to OI were analyzed and reviewed by using the whole-sequence exon gene detection technology. Results The patient′s COL1A1 gene was not found with pathogenicity variation, while the COL1A2 gene was detected with a new hybrid missense mutation (c.G2882A, p.G961D). The mutation had not been reported in PubMed and HGMD databases, which was inherited from her mother. Conclusions According to the clinical information of the children, the genetic model of disease and comprehensive evaluation of Exomiser software, it is predicted that the new mutation of COL1A2 gene (c.G2882A, p.G961D) is the cause of OI in this case.
关键词
成骨不全症 /
C0L1A2 基因 /
新突变
Key words
osteogenesis imperfecta /
COL1A2 gene /
new mutation
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Forlino A, Marini JC.Osteogenesis imperfecta[J]. Lancet,2016,387(10028):1657-1671.
[2] 余长缨,王午喜,韩德宣.成骨不全的诊治进展[J]. 中国儿童保健杂志,2014,22(2):156-158.
[3] Forlino A, Cabral WA, Barnes AM, et al.New perspectives on osteogenesis imperfecta[J]. Nat Rev Endocrinol,2011,7(9):540-557.
[4] 鲁艳芹, 任秀智,王延宙, 等.成骨不全及其分子机制[J]. 生物化学与生物物理进展,2015,42(6):511-518.
[5] Glorieux FH.Osteogenesis imperfecta[J]. Best Pract Res Clin Rheumatol,2008,22(1):85-100.
[6] Marini JC, Forlino A, Cabral WA, et al.Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen:regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans[J]. Hum Mutat,2007,28(3):209-221.
[7] Steiner RD, Adsit J, Basel D.COL1A1/2-related osteogenesis imperfecta[M].//Adam MP, Ardinger HH, Pagon RA, et al. Gene Reviews,Seattle(WA):University of Washington,1993-2018.
[8] 郑峰.成骨不全家系分析并文献复习[J]. 中国全科医学,2012, 15(2):536-537.
[9] 吕芳, 李梅.成骨不全症治疗新药研究进展[J]. 国际药学研究杂志,2017, 44(2):173-176.
[10] Pereira R, Halford K, Sokolov BP,et al.Phenotypic variability and incomplete penetrance of spontaneous fractures in an inbred strain of transgenic mice expressing a mutated collagen gene[J]. J Clin Invest, 1994, 93(4):1765-1769.
PDF(1444 KB)
