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目的 检测并分析一例肾-视神经乳头缺损综合征(RCS)患儿的基因突变位点.方法 一例表现为右眼先天性白内障、左眼视盘缺损的患儿及其正常表型的父母纳入研究.采集3名受试者的外周静脉血,提取基因组DNA.应用二代测序法筛查、Sanger测序法验证PAX2基因突变位点.通过相关数据库和PubMed文献检索基因突变位点的致病性报道.结合患者临床表现和相关检查结果,根据《遗传变异分类标准与指南》判断该基因突变的致病性.根据基因突变结果针对性行肾脏彩色超声和肾功能检查.结果 该息儿存在PAX2基因c.70dupG(p.V26Gfs*28)杂合突变,导致PAX2基因的编码蛋白转录因子配对盒2的第26位氨基酸由缬氨酸突变为甘氨酸并移码28个密码子后终止翻译.正常表型的父母均不携带此突变.Sanger测序法验证结果显示,息儿及其父母的PAX2基因突变情况与二代测序一致.患儿疾病表型推断为PAX2基因c.70dupG(p.V26Gfs*28)杂合突变所致,系常染色体显性遗传.肾脏彩色超声检查发现,患儿左肾小囊肿及集合系统轻度分离.肾功能检查结果显示,患儿α1微球蛋白指标升高.结论 PAX2基因c.70dupG(p.V26Gfs*28)杂合突变是该患儿的致病原因.

Objective To analyze and identify the pathogenic mutation that caused a case of child's renal coloboma syndrome (RCS).Methods A child with congenital cataract in the right eye and optic disc defect in the left eye and his parents with normal phenotype were included in the study.The blood of the child and his parents were captured to extract DNA and make molecular test.The possible variants were screened through NGS sequencing using the ophthalmology gene panel on illumina NextSeq 500 platform,and proved the selected PAX2 mutation by Sanger sequencing.Pathogenicity report was retrieved through PubMed and related database.Pathogenicity analysis of the candidate mutated site has careful consideration of the patient's clinical presentations and sequencing result base on Standards and Guidelines for the Interpretation of Sequence Variants revised by ACMG.According to the results of gene diagnosis,the child was executed related clinical examinations on kidney.Results The sequence result showed that a heterozygous mutation in PAX2,c.70dupG (p.V26Gfs*28),which lead to truncated protein product that terminated after 28 amino acids of the mutated site.Both of his normal parents were not carriers of the heterozygous mutation.Sanger sequencing results of the child and his parents were consistent with the NGS sequencing.The autosomal dominant disease phenotype was inferred to be caused by the heterozygous mutation of c.70dupG (p.V26Gfs*28) of PAX2 gene.Renal color Doppler ultrasound results showed the child with small renal cysts on the left and mildly separated collecting system.Renal function tests showed the child with αl microglobulin index increased.Conclusion The heterozygous mutation c.70dupG (p.V26Gfs*28) in PAX2 is the genetic pathogenic cause for the patient with RCS.