摘要目的 了解6例瓜氨酸血症患儿相关致病基因突变情况.方法 应用MassArray技术结合Sanger测序法对6例瓜氨酸血症患儿ASS1、ASL和SLC25A13基因进行突变分析,寻找可能的致病突变位点.结果 6例瓜氨酸血症患儿中,1例患儿检测到ASL基因c.1311T＞G(p.Y437*)纯合突变,确诊为精氨酰琥珀酸尿症;其余5例患儿分别检测到SLC25A13基因c.851_854delGTAT纯合突变、c.851_854delGTAT和IVS6+5G＞A复合杂合突变、c.851_854delGTAT和IVS16ins3Kb复合杂合突变、c.851_854delGTAT和IVS6-11A＞G复合杂合突变、c.851_854delGTAT和c.1638_1660dup23复合杂合突变,确诊为citrin缺陷导致的新生儿肝内胆汁淤积症.其中,ASL基因c.1311T＞G在中国人群尚未见报道,SLC25A13基因IVS6-11A＞G突变为未报道过的新突变,HSF软件预测结果显示该变异很可能导致剪接异常.结论 通过相关致病基因分析,从基因水平上证实了6例瓜氨酸患儿的诊断,发现1个新的突变位点,丰富了瓜氨酸血症致病基因的突变谱.

abstractsObjective To detect potential mutations in six patients with citrullinemia.Methods Genomic DNA was extracted from peripheral blood samples from the patients.Mutations of the ASS1,ASL and SLC25A13 genes were screened using microarray genotyping combined with direct sequencing.Results One patient was diagnosed with argininosuccinate lyase deficiency,and has carried a homozygous c.1311T＞G (p.Y437 *) mutation of the ASL gene.The remaining five patients were diagnosed with neonatal intrahepatic cholestasis due to citrin deficiency,and have respectively carried mutations of the SLC25A13 gene including [c.851 _854delGTAT+ c.851 _854delGTAT],[c.851 _854delGTAT t IVS6 + 5G＞ A],[c.851_854delGTAT+IVS16ins3Kb],[c.851_854delGTAT+IVS6-11A＞G] and [c.851_854delGTAT+c.1638_1660dup23].Among these,the c.1311T＞ G mutation was first identified in the Chinese population,and the IVS6-11A＞G mutation was a novel variation which may affect the splicing,as predicted by Human Splicing Finder software.Conclusion This study has confirmed the molecular diagnosis of citrullinemia in six patients and expanded the mutational spectrum underlying citrullinemia.