摘要
目的通过检测1例中国Crigler—NajjarI型综合征（CN—I）患者及其家系的尿苷二磷酸葡萄糖醛酸转移酶基因（UGT1A1）突变，分析该家系的基因遗传特点。方法研究对象为1个CN—I先证者及其家系成员；健康对照人群为50例血清胆红素水平正常的足月新生儿。提取研究对象基因组DNA，应用聚合酶链反应（PCR）法分别扩增UGT1A1基因的启动子及全部外显子，通过直接测序法检测UGT1A1基因突变。结果先证者及其流产胞妹UGT1A1基因第1外显子第715密码子发生了C〉T纯合子无义突变，导致编码谷氨酰胺的密码子变为终止密码子（Q239x），其余家系成员中4例为该突变的杂合子，1名第715密码子为野生型。该家系同时检测到另外2个位于UGT1A1第1外显子上的突变位点：TA盒插入突变和G71R（211G〉A）错义突变。先证者及其流产胞妹为TA盒的A（TA）7TAA纯合突变，其余4例家系成员为该突变杂合子，1例为TA盒野生型；先证者的3例家系成员为G71R杂合突变，而先证者及另外3例家系成员为G71R野生型。第2～5外显子未检测出突变，50例健康对照新生儿未检测出以上突变。结论Q239x纯合突变是本例Crigler—Najjar综合征家系的致死基因；协同G71R、A（TA）7TAA突变可能进一步降低UGT1A1酶活性，引起不同程度的胆红素代谢障碍。
Objective To test the mutation locus of uridine diphospho-glucuronosyltransferase gene （UGTIA1） in a Chinese patient with Crigler-Najjar syndrome type I and her family members, analyzing the genetic characteristics of the pedigree. Methods Genomic DNA was extracted from the patient and her family members and other 50 full-term infants with normal serum bilirubin as a healthy control group. Fifty cases of full-term newborn whose serum bilirubin level were nomal were study as controls. The promoter and all exons of UGTIA1 gene were amplified by the method of polymerase chain reactions （PCR） , and mutations were identified by direct sequencing. Results The propositus and her miscarriage sister were homozygous for a nonsense mutation at nucleotide number 715 （715C 〉 T） in exon 1 of gene UGTIA1, substituting of stop codon （TAG） for glutamine （CAG） at position 239 （ Q239X）. The other 5 members were heterozygous in the same mutation locus. A TA insertion mutation and a G71R mutation in exon 1 were observed in the family members. The patient and her sister were homozygous of A （TA）7TAA mutation while other four were heterozygous. Propositus, grandmother, mother and her younger brother were heterozygous of G71 R mutation. No mutation was found in exons 2 - 5. No mutation was found in other fifty healthy cases in the healthy control group. Con- dusions Q239X homozygons mutations is considered to be the lethal gene in this Crigler-Najjar syndrome family. Col- laborative G71 R and A（ TA）7TAA mutations may further reduce the enzyme activity of UGT1 A1, causing varying de- grees of bilirubin disorder.
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2014年第11期847-850,共4页
Chinese Journal of Applied Clinical Pediatrics
基金
国家自然科学基金（81060055）
广西自然科学基金（0728117）
