【摘要】 目的:对3个血友病B家系进行凝血因子Ⅸ(F9)基因突变分析,并对家系中的4个高危胎儿行产前诊断。方法:采用PCR反应和扩增后DNA直接测序技术对3个家系先证者及其家系成员F9基因的8个外显子进行序列分析,确定先证者及携带者的基因型后取羊水或绒毛进行产前诊断。结果:3个家系患者中均检出了F9基因突变,分别为G79R(c.10487G>A)、17788DelG、IVS2+4A>T(c.6493A>T)突变,其中,17788DelG为国内外首次报道的突变。女性携带者中检测出上述位点的杂合突变。家系1和家系2中行产前诊断的男性胎儿未携带F9基因突变,家系3中女性胎儿携带有IVS2+4A>T杂合突变,出生后随访均证实产前诊断的结果。结论:F9基因G79R、17788DelG、IVS2+4A>T是3个血友病B家系的致病性突变,应用基因测序技术可以对血友病B家系行有效的基因和产前诊断。更多还原

【Abstract】 Aim:To identify the mutations of factor Ⅸ(F9) gene and provide prenatal diagnosis in three pedigrees with haemophilia B (HB).Methods:Eight coding exons of F9 gene in patients with HB and the relative family members were amplified by PCR. The products were further analyzed by direct sequencing. Prenatal genetic diagnosis was performed by amniocentesis or by chorionic villus sampling after the genotypes of the probands and female carriers were identified.Results:Different mutations of F9 gene were detected in each pedigree, including G79R (c.10487G>A), 17788DelG and IVS2+4A>T (c.6493A>T). It was the first time that 17788DelG was reported worldwide. Heterozygous double peaks at the same position were found in female carriers. In pedigrees 1 and 2, the male fetuses were not found mutation of F9 gene, and the female fetus in pedigree 3 was heterozygous carrier of IVS2+4A>T.Conclusion:These three types of mutation of F9 gene may be the pathologic cause of the three pedigrees with HB. Direct sequencing of F9 gene is a rapid method to provide genetic counseling, prenatal diagnosis and carriers screening for HB.更多还原