CAJ | 학술논문

目的建立脊肌萎缩症(spinal muscular atrophy,SMA)携带者筛查的技术体系,评估上海地区SMA携带者频率和携带者筛查的检出效率.方法收集经临床和分子确诊的15例SMA患儿以及38个SMA核心家庭的76名患儿父母的样本,建立荧光定量PCR检测SMN1拷贝数的技术体系,对上海地区1741名无症状孕妇进行SMA携带者筛查,根据Hardy Weinberg平衡定律,计算SMN1等位基因频率.结果 1741名无症状孕妇中共检出SMN1拷贝数为1的SMA携带者45例,0-拷贝、1-拷贝、2拷贝、3-拷贝等位基因频率分别为1.37×10-2、9.45×10-1、2.80×10-2、1.27×10-2,调整后的SMA携带者比率为1∶35,筛查检出率为94.49％.携带者筛查结果阴性的个体,3拷贝的筛查后残留风险相对较高.结论上海地区SMA携带者发生率与高加索人群相近,携带者筛查具有较高检出率.本研究结果提示,携带者筛查中对于SMN1拷贝数超过2的多拷贝数有必要进一步区分,以获得2-拷贝和3-拷贝等位基因的准确频率,这些数据对于筛查后残留风险的遗传咨询十分重要.
목적 건립척기위축증(spinal muscular atrophy,SMA)휴대자사사적기술체계,평고상해지구SMA휴대자빈솔화휴대자사사적검출효솔.방법 수집경림상화분자학진적15례SMA환인이급38개SMA핵심가정적76명환인부모적양본,건립형광정량PCR검측SMN1고패수적기술체계,대상해지구1741명무증상잉부진행SMA휴대자사사,근거Hardy Weinberg평형정률,계산SMN1등위기인빈솔.결과 1741명무증상잉부중공검출SMN1고패수위1적SMA휴대자45례,0-고패、1-고패、2고패、3-고패등위기인빈솔분별위1.37×10-2、9.45×10-1、2.80×10-2、1.27×10-2,조정후적SMA휴대자비솔위1∶35,사사검출솔위94.49％.휴대자사사결과음성적개체,3고패적사사후잔류풍험상대교고.결론 상해지구SMA휴대자발생솔여고가색인군상근,휴대자사사구유교고검출솔.본연구결과제시,휴대자사사중대우SMN1고패수초과2적다고패수유필요진일보구분,이획득2-고패화3-고패등위기인적준학빈솔,저사수거대우사사후잔류풍험적유전자순십분중요.
Objective To develop a screening program for spinal muscular atrophy (SMA) carriers,and to assess the carrier frequency and detection rate in Shanghai region.Methods Quantitative analysis of the SMN1 gene by real-time PCR was developed using specimens from 15 SMA patients and 76 SMA parents from 38 affected nuclear families.A pilot screening was carried out for 1741 asymptomatic pregnant women.Frequencies of SMN1 alleles were determined with the Hardy-Weinberg equilibrium.Results Forty-five out of the 1741 women were identified as SMA carriers by the presence of single copy of SMN1.The frequencies of no-copy,1-copy,2-copy and 3-copy alleles were 1.37×10-2,9.45×10-1,2.80×10-2 and 1.27×10-2,respectively.The adjusted SMA carrier frequency was 1 ∶ 35 with a detection rate of 94.49％.For those with a negative screening result,individuals with 3 copies carried a higher residual risk.Conclusion The incidence of SMA carriers in Shanghai region is similar with that in Caucasian populations.Carrier screening has high detection efficiency.An effort should be made to further distinguish SMN1 gene copy numbers for those with ≥2 copies,since accurate determination of 2-and 3-copy allele frequencies is essential for postscreening genetic consulting.