摘要
目的建立脊肌萎缩症（spinalmuscularatrophy，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SMNI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SMNl等位基因频率。结果1741名无症状孕妇中共检出SMNl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SMNl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。
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-copyand3-copyalleleswerel. 37×10-2, 9.45×10-1, 2.80×10-2 and1.27×10 -2, respectively. The adjusted SMA carrier frequency was 1 ： 35 with a detection rate of 94. 490/00. 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 post- screening genetic consulting.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2013年第1期1-4,共4页
Chinese Journal of Medical Genetics
基金
上海市卫生局青年项目基金（2010Y114）
