分子遗传学检查诊断Crigler-Najjar综合征Ⅱ型3例

目的 探讨采用分子遗传学检查诊断Crigler-Najjar综合征Ⅱ型的方法。方法 在本科收治的3例高间接胆红素血症患者，抽取外周静脉血，提取基因组DNA，应用PCR法扩增尿苷二磷酸葡萄糖醛酸转移酶1A1基因（UGT1A1）所含5个外显子及其侧翼序列，进行DNA直接测序。结果 3例患者均检出UGT1A1基因5号外显子存在c. 1456 T>G（p.Y486D）纯合突变；Y486D位于第5外显子上，使1456位胸腺嘧啶（T）突变为鸟嘌呤（G），导致486位氨基酸由酪氨酸（Tyr）变为天冬氨酸（Asp）。结论 当临床上高度怀疑Crigler-Najjar综合征Ⅱ型时，应尽早行分子遗传学检查，确定其基因突变位点，以明确诊断。

Mutation of uridine diphosphate glucuronosyltransferase in three patients with Crigler-Najjar syndrome type II

Objective To investigate the diagnosis of patients with Crigler-Najjar syndrome type II （CN-II）. Methods Three patients with sustained unconjugated hyperbilirubinemia were admitted to our Department of Infectious Diseases，First Affiliated Hospital，Nanjing Medical University. The blood genome DNA was extracted，and five exons and their flanking sequences of uridine diphosphate glucuronosyltransferase 1A1 gene（UGT1Al） were amplified by polymerase chain reaction and the products were directly sequenced. Results Substitution of thymine for guanine at loci 1456 in the 5th exon existed leading to the change of amino acid from tyrosine to aspartate at 486th position of the corresponding protein（c．1456T>G：p．Y486D）． So the three patients were confirmed with CN-Ⅱ． Conclusions A given patient with sustained unconjugated hyperbilirubinemia should be applied early to the gene analysis for the diagnosis of Crigler-Najjar syndrome.