中华皮肤科杂志
中華皮膚科雜誌
중화피부과잡지
Chinese Journal of Dermatology
2009年
8期
569-571
,共3页
周少娜%彭振辉%肖生祥%李晓莉%刘艳%李伯埙
週少娜%彭振輝%肖生祥%李曉莉%劉豔%李伯壎
주소나%팽진휘%초생상%리효리%류염%리백훈
原卟啉病,红细胞生成性%亚铁螯合酶%DNA突变分析
原卟啉病,紅細胞生成性%亞鐵螯閤酶%DNA突變分析
원계람병,홍세포생성성%아철오합매%DNA돌변분석
Protoporphyria,erythropoietic%Ferrochelatase%DNA mutational analysis
目的 对一红细胞生成性原卟啉病(EPP)家系进行基因突变研究,探讨基因突变与临床表现的关系,为进一步开展基因诊断和基因治疗奠定基础.方法 收集家系资料,抽取家系中患者、正常人及与该家系无关的50例正常人的外周血,提取外周血基因组DNA.应用PCR方法 扩增外周血基因组DNA亚铁螯合酶(FECH)基因的第1至11外显子及其侧翼序列.PCR产物直接进行双向测序以检测突变.结果 根据临床表现和卟啉测定结果 ,患者明确诊断为红细胞生成性原卟啉病.PCR扩增得到预期DNA片段.PCR产物直接测序结果 :家系中先证者、其妹和其父FECH基因第1内含子供体剪接位点检测到一个杂合突变(IVS1+1G→G),该突变为国际首次报道.还在先证者、其妹和其母FECH基因第1内含子受体端检测到一个与低表达等位基因相关的多态性(IVS1-23C/T).结论 报道一FECH基因第1内含子供体剪接位点的新突变,该突变可能引发FECH基因缺陷,是EPP家系中患者发病的分子基础.
目的 對一紅細胞生成性原卟啉病(EPP)傢繫進行基因突變研究,探討基因突變與臨床錶現的關繫,為進一步開展基因診斷和基因治療奠定基礎.方法 收集傢繫資料,抽取傢繫中患者、正常人及與該傢繫無關的50例正常人的外週血,提取外週血基因組DNA.應用PCR方法 擴增外週血基因組DNA亞鐵螯閤酶(FECH)基因的第1至11外顯子及其側翼序列.PCR產物直接進行雙嚮測序以檢測突變.結果 根據臨床錶現和卟啉測定結果 ,患者明確診斷為紅細胞生成性原卟啉病.PCR擴增得到預期DNA片段.PCR產物直接測序結果 :傢繫中先證者、其妹和其父FECH基因第1內含子供體剪接位點檢測到一箇雜閤突變(IVS1+1G→G),該突變為國際首次報道.還在先證者、其妹和其母FECH基因第1內含子受體耑檢測到一箇與低錶達等位基因相關的多態性(IVS1-23C/T).結論 報道一FECH基因第1內含子供體剪接位點的新突變,該突變可能引髮FECH基因缺陷,是EPP傢繫中患者髮病的分子基礎.
목적 대일홍세포생성성원계람병(EPP)가계진행기인돌변연구,탐토기인돌변여림상표현적관계,위진일보개전기인진단화기인치료전정기출.방법 수집가계자료,추취가계중환자、정상인급여해가계무관적50례정상인적외주혈,제취외주혈기인조DNA.응용PCR방법 확증외주혈기인조DNA아철오합매(FECH)기인적제1지11외현자급기측익서렬.PCR산물직접진행쌍향측서이검측돌변.결과 근거림상표현화계람측정결과 ,환자명학진단위홍세포생성성원계람병.PCR확증득도예기DNA편단.PCR산물직접측서결과 :가계중선증자、기매화기부FECH기인제1내함자공체전접위점검측도일개잡합돌변(IVS1+1G→G),해돌변위국제수차보도.환재선증자、기매화기모FECH기인제1내함자수체단검측도일개여저표체등위기인상관적다태성(IVS1-23C/T).결론 보도일FECH기인제1내함자공체전접위점적신돌변,해돌변가능인발FECH기인결함,시EPP가계중환자발병적분자기출.
Objective To investigate the FECH gene mutation in a Chinese family with erythropoietic protoporphyria, to explore the relationship between gene mutation and clinical manifestations so as to estab-lish a basis for the genetic diagnosis and treatment of erythropoietic protoporphyria. Methods Clinical data on a Chinese family with typical EPP was collected. Peripheral blood was obtained from patients, unaffected individuals in the family and 50 unrelated human controls. Genomic DNA was extracted and PCR was per-formed to amplify the whole coding regions (exons 1 to 11) of FECH gene and their flanking intron sequences followed by direct sequencing to detect possible mutations. Results Based on clinical symptom and por-phyrin levels, a diagnosis of erythropoietic protoporphyria was made in 3 family members. DNA fragments of expected size were amplified by PCR. Gene sequencing revealed a heterozygons mutation (IVS1 + 1G >C) in intron 1 of FECH gene in the proband, his sister and father, but not in unaffected family members or unrelated human controls. Also, an IVS1-23C/T polymorphism associated with low expression alleles was observed in intron 1 of FECH gene of the proband, his sister and mother. Conclusions A novel mutation in the donor splice site of intron 1 of FECH gene is first reported in a Chinese family with EPP; this muta-tion may lead to a deficiency of FECH gene and serve as a molecular basis of development of erythropoietic protoporphyria.