Objectives: To investigate the genotypes of the pathogenic gene COL4A5 and the characteristics of clinical phenotypes in children with Alport syndrome (AS).
Methods: A retrospective analysis was performed for the genetic testing results and clinical data of 19 AS children with COL4A5 gene mutations.
Results: Among the 19 children with AS caused by COL4A5 gene mutations, 1 (5%) carried a new mutation of the COL4A5 gene, i.e., c.3372A>G(p.P1124=) and presented with AS coexisting with IgA vasculitis nephritis; 3 children (16%) had large fragment deletion of the COL4A5 gene, among whom 2 children (case 7 had a new mutation site of loss51-53) had gross hematuria and albuminuria at the onset, and 1 child (case 13 had a new mutation site of loss3-53) only had microscopic hematuria, while the other 15 children (79%) had common clinical phenotypes of AS, among whom 7 carried new mutations of the COL4A5 gene. Among all 19 children, 3 children (16%) who carried COL4A5 gene mutations also had COL4A4 gene mutations, and 1 child (5%) had COL4A3 gene mutations. Among these children with double gene mutations, 2 had gross hematuria and proteinuria at the onset.
Conclusions: This study expands the genotype and phenotype spectrums of the pathogenic gene COL4A5 for AS. Children with large fragment deletion of the COL4A5 gene or double gene mutations of COL4A5 with COL4A3 or COL4A4 tend to have more serious clinical manifestations.
目的: 探讨儿童Alport综合征（Alport syndrome，AS）致病基因COL4A5基因型与临床表型的特点。方法: 回顾性分析19例存在COL4A5基因突变的AS患儿的基因检测结果和临床资料。结果: 19例COL4A5基因突变导致的AS患儿中，1例（5%）存在COL4A5基因新突变位点c.3372A>G(p.P1124=)，其表现为AS合并IgA血管炎肾炎；3例（16%）存在COL4A5基因大片段缺失，其中2例（例7为新突变位点：loss51-53）起病即存在肉眼血尿和蛋白尿，1例（例13，存在新突变位点：loss3-53）仅有镜下血尿；其余15例（79%）患儿均为AS的常见临床表型，其中7例存在COL4A5基因新突变位点。3例（16%）患儿合并COL4A4基因突变，1例（5%）合并COL4A3基因突变，在这些双基因突变患儿中有2例起病即为肉眼血尿合并蛋白尿。结论: 该研究拓展了AS致病基因COL4A5的基因型和表型谱；发生COL4A5基因大片段缺失突变或COL4A5合并COL4A3或COL4A4的双基因突变患儿的临床表现更严重。.
Keywords: Alport syndrome; COL4A5 gene; Child; Clinical phenotype; Genotype.