摘要
目的分析1个非溶血性未结合胆红素增高黄疸家系的尿苷二磷酸葡萄糖醛酸转移酶(UGT1A1)基因突变情况。方法选择河南省濮阳市油田总医院儿科2010年11月收治的1例持续非溶血性高未结合胆红素血症患儿为研究对象,对该患儿及其家族成员UGT1A1基因的5个外显子以及外显子与内含子连接区域进行DNA序列分析。结果先证者UGT1A1基因存在3个突变位点,即第1外显子第211位的鸟嘌呤(G)转换为腺嘌呤(A),导致编码蛋白第71位甘氨酸(Gly)变为精氨酸(Arg),即211G>A(G71R);为杂合改变;5号外显子第1 456位的胸腺嘧啶(T)颠换为鸟嘌呤(G),导致编码蛋白第486位酪氨酸(Tyr)变为天门冬氨酸(Asp),即1 456T>G(Y486D),为纯合突变,根据临床表现,诊断为Crigler-Najjar综合征Ⅱ型,其祖父和其父亲婴儿期有反复黄疸病史,UGT1A1基因存在2个突变位点,即211G>A(G71R)和1 456T>G(Y486D),均为杂合改变。结论对于临床上持续未结合胆红素增高的患者,进行UGT1A1基因突变分析能明确诊断。
Objective To analyze and determine the gene mutation of uridine diphosphate glucuronosyl-transferasel A1gene（ UGT1A1） in a family with unconjugated hyperbilirubinemia. Methods A child with sustained unconjugated hyperbilirubinemia from Department of Pediatric of Puyang Oil Field General Hospital in October 2011 was admitted in the study. The genome DNA was extracted. Five exons and linking-regions between exons and introns of UGTIAl were amplified and sequenced. Results Sequence analysis of the proband revealed adenine for guanine mutation at loci 211 in the one exon casusing glycine-to-arginine mutation at the 71 position of the corresponding protein： 211 G A（ G71R）; Substitution of thymine for guanine at loci 1 456 in the 5 exon changed the amino acid from tyrosine to aspartate at 486 position of the corresponding protein： 1 456 T G（ Y486D）. So the patient was confirmed with CN-Ⅱ. Both 211 G A（ G71R） and 1 456 T G（ Y486D） heterozygosis mutation in UGT1A1 gene were detected in his grandfather and father,and they had mild jaundice interval. Conclusion The application of genetic test can help early diagnosis of the disease for child with sustained unconjugated hyperbilirubinemia.
出处
《新乡医学院学报》
CAS
2016年第7期603-605,609,共4页
Journal of Xinxiang Medical University
