中华实用儿科临床杂志
中華實用兒科臨床雜誌
중화실용인과림상잡지
Journal of Applied Clinical Pediatrics
2014年
11期
847-850
,共4页
冯于玲%高宗燕%刘义%钟丹妮
馮于玲%高宗燕%劉義%鐘丹妮
풍우령%고종연%류의%종단니
Crigler-Najjar综合征%新生儿黄疸%尿苷二磷酸葡萄糖醛酸转移酶%突变%家系
Crigler-Najjar綜閤徵%新生兒黃疸%尿苷二燐痠葡萄糖醛痠轉移酶%突變%傢繫
Crigler-Najjar종합정%신생인황달%뇨감이린산포도당철산전이매%돌변%가계
Crigler-Najjar syndrome%Neonatal jaundice%Uridine diphospho-glucuronosyltransferase%Mutation%Pedigree
目的 通过检测1例中国Crigler-Najjar Ⅰ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.
目的 通過檢測1例中國Crigler-Najjar Ⅰ型綜閤徵(CN-Ⅰ)患者及其傢繫的尿苷二燐痠葡萄糖醛痠轉移酶基因(UGT1A1)突變,分析該傢繫的基因遺傳特點.方法 研究對象為1箇CN-Ⅰ先證者及其傢繫成員;健康對照人群為50例血清膽紅素水平正常的足月新生兒.提取研究對象基因組DNA,應用聚閤酶鏈反應(PCR)法分彆擴增UGT1A1基因的啟動子及全部外顯子,通過直接測序法檢測UGT1A1基因突變.結果 先證者及其流產胞妹UGT1A1基因第1外顯子第715密碼子髮生瞭C＞T純閤子無義突變,導緻編碼穀氨酰胺的密碼子變為終止密碼子(Q239X),其餘傢繫成員中4例為該突變的雜閤子,1名第715密碼子為野生型.該傢繫同時檢測到另外2箇位于UGT1A1第1外顯子上的突變位點:TA盒插入突變和G71R(211G＞ A)錯義突變.先證者及其流產胞妹為TA盒的A(TA)7TAA純閤突變,其餘4例傢繫成員為該突變雜閤子,1例為TA盒野生型;先證者的3例傢繫成員為G71R雜閤突變,而先證者及另外3例傢繫成員為G71R野生型.第2～5外顯子未檢測齣突變,50例健康對照新生兒未檢測齣以上突變.結論 Q239X純閤突變是本例Crigler-Najjar綜閤徵傢繫的緻死基因;協同G71R、A(TA)7TAA突變可能進一步降低UGT1A1酶活性,引起不同程度的膽紅素代謝障礙.
목적 통과검측1례중국Crigler-Najjar Ⅰ형종합정(CN-Ⅰ)환자급기가계적뇨감이린산포도당철산전이매기인(UGT1A1)돌변,분석해가계적기인유전특점.방법 연구대상위1개CN-Ⅰ선증자급기가계성원;건강대조인군위50례혈청담홍소수평정상적족월신생인.제취연구대상기인조DNA,응용취합매련반응(PCR)법분별확증UGT1A1기인적계동자급전부외현자,통과직접측서법검측UGT1A1기인돌변.결과 선증자급기유산포매UGT1A1기인제1외현자제715밀마자발생료C＞T순합자무의돌변,도치편마곡안선알적밀마자변위종지밀마자(Q239X),기여가계성원중4례위해돌변적잡합자,1명제715밀마자위야생형.해가계동시검측도령외2개위우UGT1A1제1외현자상적돌변위점:TA합삽입돌변화G71R(211G＞ A)착의돌변.선증자급기유산포매위TA합적A(TA)7TAA순합돌변,기여4례가계성원위해돌변잡합자,1례위TA합야생형;선증자적3례가계성원위G71R잡합돌변,이선증자급령외3례가계성원위G71R야생형.제2～5외현자미검측출돌변,50례건강대조신생인미검측출이상돌변.결론 Q239X순합돌변시본례Crigler-Najjar종합정가계적치사기인;협동G71R、A(TA)7TAA돌변가능진일보강저UGT1A1매활성,인기불동정도적담홍소대사장애.
Objective To test the mutation locus of uridine diphospho-glucuronosyltransferase gene (UGT1A1) 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 UGT1A1 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 UGT1A1,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.Conclusions Q239X homozygous mutations is considered to be the lethal gene in this Crigler-Najjar syndrome family.Collaborative G71 R and A(TA)7TAA mutations may further reduce the enzyme activity of UGT1A1,causing varying degrees of bilirubin disorder.
