营养不良型大疱性表皮松解症1家系COL7A1基因诊断和产前诊断

发布时间：2018-07-10 06:52

本文选题：营养不良型大疱性表皮松解症 + COLA基因　；参考：《中国皮肤性病学杂志》2016年09期

【摘要】：目的分析常染色体显性遗传的营养不良型大疱性表皮松解症(DDEB)1家系的致病基因COL7A1基因突变位点,并在此基础上探讨产前诊断的可行性。方法采用聚合酶链扩增反应及双向直接测序的方法对DDEB家系中2例不同表型的患者进行COL7A1基因突变检测,以家系中的2例健康者及50例无亲缘关系的健康个体作对照。确定致病突变后,对家系中的2例高危胎儿分别进行了产前遗传学分析和胎儿绒毛组织DNA产前诊断。结果该家系2名不同表型患者COL7A1基因的87号外显子第6859位碱基鸟嘌呤G被腺嘌呤A替代(c.6859GA,p.Gly2287Arg),家系中健康对照及无亲缘关系的健康个体均未发现该突变。先证者姐姐怀孕4周,被证明未携带致病突变,继续妊娠并诞生一个健康男婴。先证者配偶怀孕11周,产前诊断胎儿携带与患者相同的突变。先证者夫妇选择治疗性引产术后,取胎儿皮肤标本行基因诊断,结果与产前诊断相同。结论甘氨酸替代突变c.6859GA,(p.Gly2287Arg)是该DDEB家系的致病原因,同一家系患者呈现不同表型。COL7A1基因分析可以快速且准确地进行DDEB的基因诊断和产前诊断,有利于指导生育健康后代。
[Abstract]:Objective to analyze the mutation site of COL7A1 gene in an autosomal dominant dystrophy type epidermolysis bullosa (DDEB) family, and to explore the feasibility of prenatal diagnosis. Methods Polymerase chain reaction (PCR) and bidirectional direct sequencing were used to detect COL7A1 gene mutation in 2 DDEB families with different phenotypes, 2 healthy individuals and 50 unrelated healthy individuals were used as controls. After identifying the pathogenic mutation, two high-risk fetuses in the family were analyzed for prenatal genetics and prenatal diagnosis of fetal chorionic DNA. Results this mutation was replaced by adenine A (c. 6859 GAp.Gly2287Arg) at exon 6859 of COL7A1 gene in two patients with different phenotypes. The mutation was not found in healthy controls and unrelated healthy individuals. The proband sister, who was 4 weeks pregnant, was found not to carry a mutation, continued pregnancy and gave birth to a healthy baby boy. The proband's spouse is 11 weeks pregnant and the prenatal diagnosis of the fetus carries the same mutation as the patient. The proband and his wife chose the therapeutic induction of labor after operation, take the fetal skin samples for gene diagnosis, the results are the same as prenatal diagnosis. Conclusion glycine substitution mutation c.6859GA (p.Gly2287Arg) is the causative cause of DDEB. The gene analysis of different phenotypes of .COL7A1 in the same family can quickly and accurately diagnose DDEB gene and prenatal diagnosis, which is helpful to guide healthy offspring.
【作者单位】：浙江大学医学院附属第一医院皮肤科;浙江大学医学院附属第一医院北仑分院皮肤科;浙江大学医学院附属妇产医院检验科;深圳市南山人民医院皮肤科;
【基金】：国家自然科学基金(30800989,81271743) 浙江省公益性技术应用研究计划项目(2014C33193)
【分类号】：R758.59

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