Crigler-Najjar综合征Ⅱ型UGT1A1基因突变一例报道暨文献复习  

UGT1A1 gene mutation in type Ⅱ Crigler-Najjar syndrome: a case report and literature review

作　　者：潘丽丽[1] 石岩[1] 阴怀清[1] 栗红[1] 王成礼[1] 张晓佳[1] 李迎敏[1] 

机构地区：[1]山西医科大学第一医院儿科,太原030001

出　　处：《中国新生儿科杂志》2013年第3期180-183,共4页Chinese Journal of Neonatology

基　　金：山西省回国留学人员科技基金资助项目(2011-095);山西省卫生厅科技攻关基金项目(2011-018)

摘　　要：目的分析并确定一例Crigler-Najjar综合征Ⅱ型(CN-Ⅱ)患儿的尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)基因突变,并进行文献复习,为此病的诊断及早期治疗提供依据。方法对本院儿科2012年6月收治的一例持续高未结合胆红素血症的患儿提取基因组DNA,应用聚合酶链反应扩增UGT1A1所含5个外显子以及外显子与内含子连接区域进行DNA直接测序。结果先证者UGT1A1基因发现第1外显子第211位的鸟嘌呤(G)突变为腺嘌呤(A),导致甘氨酸(Gly)变为精氨酸(Arg),即c.211G>A(p.G71R);第5外显子第1456位的胸腺嘧啶(T)突变为鸟嘌呤(G),导致酪氨酸(Tyr)变为天门冬氨酸(Asp),即c.1456T>G(p.Y486D),先证者G71R和Y486D复合杂合突变,确诊为CN-Ⅱ。结论临床上高度怀疑Crigler-Najjar综合征时,使用分子遗传学方法快速明确诊断,可以为本患儿家庭提供准确的遗传咨询及产前诊断。Objective To analyze and determine the gene mutation of uridine diphosphate glucuronosyl- transferaselA1 gene （ UGTIA1 ） in a case with type II Crigler-Najjar syndrome （ CN- II ） , and review literature to provide evidence for diagnosis and early intervention for the disease. Methods A patient with sustained unconjugated hyperbilirubinemia was admitted to the Pediatric department, First Hospital of Shanxi Medical University in June, 2012. The genome DNA was extracted. Five exons and linking-regions between exons and introns of UGT1A1 were amplified by polymerase chain reaction （PCR） and then sequenced. Results Sequence analysis of the proband revealed adenine for guanine mutation at loci 211 in the 1At exon casusing glycine-to- arginine mutation at the 71th position of the corresponding protein （c. 211 G 〉 A： p. G71 R） ; Substitution of thymine for guanine at loci 1456 in the 5th exon changed the amino acid from tyrosine to aspartate at 486th position of the corresponding protein （c. 1456T 〉 G： p. Y486D） , The proband was compound heterozygote of G71R and Y486D. So the patient was confirmed with CN- 11. Conclusions When highly suspected of Crigler-Najjar syndrome, the application of genetic tests could helping achieve early diagnosis of the disease, and to further provide accurate genetic counseling and prenatal diagnosis for the family of these patients.

关 键 词：Crigler—Najjar综合征 尿苷二磷酸葡萄糖醛酸转移酶 基因突变 

分 类 号：R722.1[医药卫生—儿科]