一例Crigler-Najjar综合征Ⅱ型患儿的基因突变分析

Genetic analysis of a child affected with Crigler-Najjarsyndrome type Ⅱ

目的对1例Crigler-Najjar综合征Ⅱ型患儿的尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）基因进行突变分析，探讨其分子发病机制，为家系的遗传咨询及产前基因诊断提供依据。方法抽取患儿及其父母的外周静脉血提取基因组DNA，应用聚合酶链反应扩增UGT1A1基因的相应片段，经DNA测序法对UGT1A1基因进行突变检测，并随访患儿至3岁6个月。结果患儿为持续高未结合胆红素血症，DNA测序结果显示患儿UGT1A1基因的第1外显子存在c．610A〉G（p．Met 204 Val）杂合突变，第4外显子存在c．1091C〉T（p．Pro 364 Leu）杂合错义突变，患儿为UGT1A1基因复合突变杂合子。患儿父亲UGT1A1基因的第4外显子存在C．1091C〉T（p．Pro 364 Leu）的杂合错义突变，患儿母亲UGT1A1基因的第1外显子存在c．610A〉G（p．Met204 Val）杂合错义突变。结论UGT1A1基因第1外显子c．610A〉G、第4外显子c．1091C〉A复合杂合突变为该患儿的发病原因，为其家系的遗传咨询和产前基因诊断提供了依据。

Objective To detect potential mutation of the UGT1A1 gene in a child affected with Crigler-Najjar syndrome type Ⅱ. Methods Blood samples were collected from the patient and his parents for the extraction of genomic DNA. Potential mutation of the UGT1A1 gene was detected with polymerase chain reaction （PCR） and direct sequencing. The child was followed up until the age of 3 year and 6 month. Results The patient showed persistent unconjugated hyperbilirubinemia. Sequencing of the UGT1A1 gene has detected a rare heterozygous c, 610 A〉G （p. Met204Val） mutation in the exon 1, in addition with a heterozygous c. 1091 C〉T （p. Pro364Leu） mutation in exon 4. The two mutations were inherited from his father and mother, respectively. The patient was diagnosed with Crigler-Najjar syndrome type Ⅱ and received oral phenobarbital treatment. Conclusion The compound UGT1A1 gene mutation probably accounts for the disease in the patient manifesting persistent mild uneonjugated hyperbilirubinemia. Genetic counseling and prenatal diagnosis should be provided for his family.