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研究背景：唐氏綜合癥(Down's Syndrome)是一種因嬰兒21號染色體異常而引起的疾病。目前如果需要明確診斷是否為妊娠唐氏綜合癥患兒，需要進(jìn)行抽取胎兒血、羊水或胎盤絨毛進(jìn)行檢查，但是這些侵入性檢查對胎兒和孕婦都有一定的危險(xiǎn)。來自香港中文大學(xué)，英國倫敦國王學(xué)院醫(yī)院（King's College Hospital），深圳華大基因的研究人員在前文（Maternal Plasma DNA Sequencing Reveals the Genome-Wide Genetic and Mutational Profile of the Fetus）的基礎(chǔ)上，再次發(fā)文，提出可以通過給孕婦進(jìn)行血液DNA檢驗(yàn)篩查唐氏綜合癥風(fēng)險(xiǎn)，從而無需類似羊膜穿刺這樣的侵入性檢查。這一研究成果公布在2011年的《BMJ》雜志上。 研究成果：在最新的這篇文章中，這一研究團(tuán)隊(duì)仍然以雙末端測序技術(shù)為基礎(chǔ)，利用Illumina的GA升級版：Genome Analyzer II進(jìn)行分析。 技術(shù)手段：血液DNA測序，生物信息學(xué)分析 研究意義：目前臨床上使用的侵入性檢查，對胎兒和孕婦都有一定的危險(xiǎn)：胎兒流產(chǎn)、早產(chǎn)、宮內(nèi)感染的風(fēng)險(xiǎn)約為1％-2%。目前采用血液檢測的產(chǎn)檢只是檢測母體血清中甲型胎兒蛋白（AFP）和絨毛促進(jìn)腺激素（HGG）的濃度，并不十分可靠。通過非侵入性的血液DNA檢查，不僅避免了侵入性檢查的風(fēng)險(xiǎn)，同時(shí)還提高了檢查結(jié)果的準(zhǔn)確性，研究人員相信這將最終成為臨床使用的檢驗(yàn)手段。 點(diǎn)評： 通過檢測孕婦外周血中存在的“漂流”的胎兒DNA，進(jìn)而實(shí)現(xiàn)產(chǎn)前診斷的低風(fēng)險(xiǎn)和高準(zhǔn)確性。 參考文獻(xiàn)： Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011.342:c7401. Abstract Objectives ：To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling. Design ：Diagnostic accuracy validated against full karyotyping, using prospectively collected or archived maternal plasma samples. Setting：Prenatal diagnostic units in Hong Kong, United Kingdom, and the Netherlands. Participants ：753 pregnant women at high risk for fetal trisomy 21 who underwent definitive diagnosis by full karyotyping, of whom 86 had a fetus with trisomy 21. Intervention ：Multiplexed massively parallel sequencing of DNA molecules in maternal plasma according to two protocols with different levels of sample throughput: 2-plex and 8-plex sequencing. Main outcome measures： Proportion of DNA molecules that originated from chromosome 21. A trisomy 21 fetus was diagnosed when the z score for the proportion of chromosome 21 DNA molecules was >3. Diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were calculated for trisomy 21 detection. Results： Results were available from 753 pregnancies with the 8-plex sequencing protocol and from 314 pregnancies with the 2-plex protocol. The performance of the 2-plex protocol was superior to that of the 8-plex protocol. With the 2-plex protocol, trisomy 21 fetuses were detected at 100% sensitivity and 97.9% specificity, which resulted in a positive predictive value of 96.6% and negative predictive value of 100%. The 8-plex protocol detected 79.1% of the trisomy 21 fetuses and 98.9% specificity, giving a positive predictive value of 91.9% and negative predictive value of 96.9%. Conclusion： Multiplexed maternal plasma DNA sequencing analysis could be used to rule out fetal trisomy 21 among high risk pregnancies. If referrals for amniocentesis or chorionic villus sampling were based on the sequencing test results, about 98% of the invasive diagnostic procedures could be avoided. |
