全外显子测序检测5例青少年Gilbert综合征患者及家系验证分析

Analysis of 5 adolescent Gilbert syndrome patients by whole exome sequencing and validation of their families

目的探讨UGT1A1基因分子家系遗传在Gilbert综合征中的诊断价值。方法分析5例因总胆红素异常增高,且治疗无明显改善的青少年患者全外显子测序结果,并对5例患者及其父母进行了筛选分析得出的致病基因UGT1A1突变位点验证。结果 5例患者经全外显子测序均发现在UGT1A1基因的c.-53-52insTA和c.-3275T>G位点发生突变;2例患者还在c.211G>A(p.G71R)有突变,1例患者在c.686C>A(p.P229Q)突变。全外显子测序还检测到5例患者其他基因突变,但并未发现患者间有其他共同的基因位点突变。针对所有突变对患者及父母进行Sanger测序验证,其结果与全外显子测序结果一致。结论采用全外显子测序技术可准确锁定Gilbert综合征患者相关致病基因UGT1A1的突变位点,并且通过家系验证得以确定,有助于协助临床医生提高诊断率。

Objective To understand the value of UGT1 A1 gene molecule genetic pedigree in the diagnosis of Gilbert syndrome.Methods The whole exome sequencing results of 5 adolescent patients with abnormally increased total bilirubin and no significant improvement after treatment were analyzed.Five cases and their parents were screened to verify the mutation site of the pathogenic gene UGT1 A1.Results The whole exome sequencing showed that all the 5 patients had the UGT1 A1 gene mutations at the sites of c.-53-52 insTA and c.-3275 T>G,2 patients also had the mutations at c.211 G>A(p.G71 R) site, and one patient had a mutation of c.686 C>A(p.P229 Q) site.The whole exome sequencing also detected other gene mutations in 5 patients, but did not find other common gene mutations among the patients.Sanger sequencing verification was performed on the patients and parents for all mutations, and the verification results were consistent with the whole exome sequencing results.Conclusion Through the whole exome sequencing, the mutation site of the related pathogenic gene UGT1 A1 in Gilbert syndrome patients can be accurately locked, and it can be confirmed through family verification, which helps clinicians to improve the diagnosis rate of Gilbert syndrome.