两个Alport综合征家系的COL4A5基因变异分析  

Analysis of two Chinese pedigrees affected with Alport syndrome due to novel variants of COL4A5 gene

作　　者：郭红军[1] 刘风勋 杨自君[4] Guo Hongjun;Liu Fengxun;Yang Zijun(Department of Obstetrics and Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Department of Nephrology with Integrated Traditional Chinese and Western Medicine,the First Affiliated Hospital of Zhengzhou university,Zhengzhou,Henan 450052,China;Institute of Nephrology,Zhengzhou University,Zhengzhou,Henan 450052,China;Department of Nephrology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院妇产科,郑州450052 [2]郑州大学第一附属医院中西医结合肾病科,郑州450052 [3]郑州大学肾脏病研究所,郑州450052 [4]郑州大学第一附属医院肾脏内三科,郑州450052

出　　处：《中华医学遗传学杂志》2022年第11期1224-1227,共4页Chinese Journal of Medical Genetics

基　　金：河南省自然科学基金(222300420330)。

摘　　要：目的分析两例X连锁显性遗传Alport综合征家系的COL4A5基因变异谱,为该病的基因诊断和遗传咨询提供依据。方法应用二代测序技术并结合PCR-Sanger测序法进行基因检测,确定基因疑似致病变异后,对家系中的其他人员进行相应位点的验证,并以100名健康人样本作为对照。采用ClustalX-2.1-win软件分析氨基酸变异位点的保守性,应用SWISS-MODEL评估位点变异对蛋白质结构的影响。结果二代测序和Sanger测序显示家系1先证者及其母亲均存在COL4A5第28外显子c.2210G>A(p.Gly737Asp)杂合变异。家系2先证者及其母亲均存在COL4A5基因第44外显子c.3799G>A(p.Gly1267Ser)纯合变异。检索文献发现,两种变异均为未见报道的新变异,且100名健康对照中未发生相应变异。COL4A5基因编码的第737位和第1267位氨基酸在同源物种间高度保守。Swiss-Model预测两种变异均明显影响COL4A5蛋白的三级结构。结论COL4A5基因c.2210G>A(p.Gly737Asp)和c.3799G>A(p.Gly1267Ser)变异可能为Alport家系的遗传学病因。该结果丰富了COL4A5基因变异谱,对于Alport综合征基因型与临床表型之间的相关性和产前筛查的进一步研究具有较大意义。Objective To explore the genetic basis for two Chinese pedigrees affected with Alport syndrome.Methods Potential variants of the COL4A5 gene were screened by next generation sequencing(NGS).Candidate variants were verified by Sanger sequencing of other members from the pedigrees as well as 100 healthy controls.ClustalX-2.1-win was used to analyze the conservation of amino acid sequences.SWISS-MODEL was used for assessing the influence of variations on the protein structure.Results Two heterozygous missense variants of the COL4A5 gene,namely c.2210G>A(p.Gly737Asp)and c.3799G>A(p.Gly1267Ser),were respectively identified in the affected individuals from the two pedigrees but not among the 100 healthy controls.Neither variant was reported previously.Conclusion The c.2210G>A(p.Gly737Asp)and c.3799G>A(p.Gly1267Ser)variants of the COL4A5 gene probably underlay the Alport syndrome in these pedigrees.Above finding has enriched the spectrum of COL4A5 gene variants and provided a basis for genetic counseling and prenatal diagnosis for the families.

关 键 词：X连锁Alport综合征 COL4A5基因 变异 

分 类 号：R596.1[医药卫生—内科学] R440[医药卫生—临床医学]