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目的对有成骨不全(Osteogenesis Imperfecta,OI)孕史的患者,进行系统B超及COL1A1/COL1A2基因检测,希望建立OI患儿产前诊断方案,为OI患儿进行产前诊断提供技术保障。方法对于有OI孕史的孕妇,进行系统B超监测;根据胎儿股骨、长骨的超声影像学表现,初诊为成骨不全。抽取羊水,采用直接测序法对羊水DNA的COL1A1和COL1A2基因全编码外显子及启动子区域进行突变位点检测。检出的新突变,对孕妇夫妇及家系其他成员直接测序证实。产前诊断标本均需做母血污染鉴定。结果胎儿超声影像学表现为股骨短小,胫腓骨弯曲成角,颅骨变薄且发现多处骨折,考虑OI。STR法鉴定,羊水无母血污染。DNA序列分析结果显示COL1A1基因鉴定出19个SNP位点,没有鉴定出突变位点;COL1A2基因鉴定出13个SNP位点及第36外显子的第2180位置碱基发生错义突变位点(c.2180G>A,p.Gly727Asp)。孕妇在COL1A2基因的第36外显子亦存在错义突变位点(c.2180G>A,p.Gly727Asp),但其临床特征不一致。其他成员均未检测到Gly727Asp突变。结论有OI孕史的孕妇,采取B超和COL1A1/COL1A2基因诊断技术,可以快速、有效对高危胎儿做出确诊,为预防患病胎儿出生提供技术保障。
OBJECTIVE: To detect B-mode ultrasound and COL1A1 / COL1A2 gene in patients with history of Osteogenesis Imperfecta (OI). We hope to establish a prenatal diagnosis program for children with OI and provide technical support for prenatal diagnosis of OI. Methods For pregnant women with OI pregnancy history, B system ultrasound was performed. According to the ultrasound imaging features of the femur and long bones, the newly diagnosed as osteogenesis imperfecta. The amniotic fluid was extracted and the mutation sites were detected by direct sequencing of the full coding exons and promoter regions of COL1A1 and COL1A2 genes in amniotic fluid DNA. Detected new mutations in pregnant women and other family members and other members of the direct sequencing confirmed. Prenatal diagnostic specimens are required to identify maternal blood contamination. Results Fetal ultrasound imaging showed short femur, tibiofibular flexion angulation, thinning skull and found that multiple fractures, consider the OI. STR identification, amniotic fluid without maternal pollution. DNA sequence analysis showed that 19 SNP sites were identified by COL1A1 gene and no mutation sites were identified. COL1A2 gene identified 13 SNP sites and the 2180th base of exon 36 missense mutation sites ( c.2180G> A, p.Gly727Asp). Pregnant women in COL1A2 gene exon 36 missense mutations (c.2180G> A, p.Gly727Asp), but its clinical features are inconsistent. No Gly727Asp mutation was detected in other members. Conclusions Pregnant women with OI pregnancy history can diagnose high-risk fetus quickly and effectively by adopting B-ultrasound and COL1A1 / COL1A2 gene diagnostic techniques, providing technical support for preventing the birth of the sick fetus.