二代测序技术确诊一例Dubin-Johnson综合征

Diagnosis of a patient with Dubin-Johnson syndrome by using next generation sequencing

目的对1例皮肤持续黄染、临床诊断为肝病综合征的患儿进行临床特点和遗传学分析。方法对患儿进行临床和实验室检查。提取患儿及其父母基因组DNA,应用二代测序技术对患儿进行相关基因突变检测,对疑似致病性突变进行生物信息学分析,并对患儿及其父母进行Sanger测序验证。结果患儿皮肤黄染2月余,巩膜黄染,临床检查显示肝脏体积增大、胆红素升高。经基因检测发现患儿MRP2基因存在c.18C>A(p.C6X)和c.2556delA(移码突变)复合杂合突变,分别遗传自父亲和母亲。结论该患儿为MRP2基因c.18C>A和c.2556delA突变引起的Dubin-Johnson综合征。二代测序技术为包括Dubin-Johnson综合征在内的罕见遗传病提供了强有力的诊断工具。

Objective To explore the clinical characteristics and molecular basis for a Chinese boy affected with jaundiced skin and liver disease. Methods The patient was subjected to clinical examination and laboratory tests. Genomic DNA of the patient and his parents was extracted and analyzed by using next generation sequencing (NGS). Suspected mutations were analyzed with bioinformatic software and verified by Sanger sequencing. Results The patient had jaundice in his eyes and skin. Serum bilirubin was elevated along with hepatomegaly. Next generation sequencing showed that the patient has carried c. 18C>A (p.C6X) and c. 2556delA mutations in the MRP2 gene, which were respectively inherited from his father and mother. Conclusion The missense mutation c. 18C>A and frameshift mutation c. 2556delA probably account for the disease. NGS has provided a powerful tool for the diagnosis of rare genetic diseases including Dubin-Johnson syndrome.