COL4A5基因新无义突变致Alport综合征一家系并文献复习

A Family with Alport Syndrome Caused by a New Nonsense Mutation of COL4A5 Gene and Literature Review

摘要: 目的：分析Alport综合征患儿临床表现与基因型特点，为该病的基因诊断和家系咨询提供基础。方法：回顾分析1例Alport综合征患儿的临床资料及基因检测结果。以“COL4A5基因、Alport综合征、无义突变”为关键词，在PubMed数据库、中国期刊全文数据库及万方数据知识服务平台检索复习相关文献。结果：先证者，男性，3岁6月，1岁9月“上呼吸道感染”后出现肉眼血尿，其母有镜下血尿情况。肾穿刺活检病理显示，电镜：部分基底膜厚薄不均，阶段性基底膜致密层增厚，部分呈撕裂状和蛛网状，足突大部分融合，未见电子致密物沉积，形态考虑Alport综合征早期改变可能。基因检测显示，COL4A5基因存在的一处半合子点突变c.4978A > T (p.K1660X)，该点突变导致翻译的第1660个氨基酸由赖氨酸突变为终止密码子，产生无义突变；经家系验证分析，先证者之父、舅舅、姨外祖母该位点无变异，先证者之母、外祖母、舅外祖父该位点均存在杂合变异，外祖母存在耳聋情况，舅外祖父患有尿毒症。文献数据库未有该位点相关性报道。结论：基因检测有助于确诊Alport综合征，该家系丰富了现存Alport综合征基因突变数据库。

Abstract: Objective: To analyze the clinical manifestations and genotypic characteristics of children with Al-port syndrome, and explore a new genetic mode of Alport syndrome, so as to provide a basis for ge-netic diagnosis and family consultation of Alport syndrome. Methods: The clinical data and genetic test results of 1 case of Alport syndrome were retrospectively analyzed. With “COL4A5 gene, Alport syndrome and nonsense mutation” as keywords, relevant literatures were searched and reviewed in PubMed database, China Journal Full-text Database and Wanfang Data knowledge service plat-form. Results: The proband, male, 3 years old 6 months, 1 year old 9 months, “upper respiratory tract infection” after gross hematuria, his mother had microscopic hematuria. The pathological re-sults of renal biopsy showed that, under electron microscope, part of the basement membrane was uneven in thickness, the dense layer of the basement membrane was gradually thickened, and some were torn and spiderlike, most of the foot processes were fused, and no deposition of elec-tronic dense substance was observed. The morphology was considered as the early change of Alport syndrome. Genetic analysis showed that there was a hemizygous point mutation of COL4A5 gene, c.4978A > T (p.K1660X), which resulted in the mutation of the 1660th amino acid from lysine to stop codon, resulting in nonsense mutation. Through familial verification analysis, the father, uncle and aunt of the proband had no variation at this site, while the mother, grandmother and uncle and grandfather of the proband had heterozygous variation at this site, the grandmother had deafness, and the uncle and grandfather had uremia. No correlation of this locus was reported in literature database. Conclusion: Genetic testing is helpful for the diagnosis of Alport syndrome, and this family has enriched the existing Alport syndrome gene mutation database.