一个中国Gilbert综合征家系的临床和遗传学特征分析

Clinical and genetic analyses of UGT1A1 gene from a Chinese family with Gilbert＇s syndrome

目的 通过对1个中国Gilbert综合征家系成员临床特征分析,结合致病基因尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）基因已知突变位点鉴定,了解该病临床发病特点和分子遗传学基础.方法 在长期追踪先证者基础上,抽取先证者及其家系成员外周血,进行肝脏生化学、病原学和UGT1A1基因突变位点检测,排除相关疾病,PCR扩增启动子和外显子常见突变位点,产物直接测序鉴定基因型.结果 在该家系中,检测到3个突变位点：c.-3279T＞G、TA插入和Gly71Arg,并且C.-3279T＞G和TA插入存在连锁不平衡,其中4例患者中3例为杂合突变,1例为纯合突变,胆红素水平与UGT1A1基因型和表型相关.结论 c.-3279T＞G、TA插入和Gly71Arg突变可能与中国人群Gilbert综合征发生相关,该家系基本符合常染色体隐性遗传方式.

Objective To perform clinical and genetic pedigree analyses of a Chinese male patient with Gilbert＇s syndrome and his relatives. Methods Blood sample were collected from the proband and his relatives by liver function test, etiological examination and genetic analysis to exclude other related diseases. The phenobarbital-responsive enhancer module （PBREM） , TATA box and common mutation sites in exons of UGT1A1 gene were amplified by polymerase chain reaction （PCR） and the products screened by direct DNA sequencing. Results c. -3279T 〉 G in PBREM, TA insertion in TATA box and Gly71Arg were observed in this family. A linkage disequilibrium is also noted between c. -3279T 〉 G and TA insertion. In four affected members, three are heterozygotes and one is homozygote. The correlation between genotype and phenotype with a high serum level of unconjugated bilirubin was confirmed. Conclusion c. -3279T 〉 G in PBREM, TA insertion in TATA box and Gly71 Arg are essential for the pathogenesis of Gilbert＇s syndrome in this Chinese family. Gilbert＇s syndrome in this family is inherited in an autosomal recessive manner.