Evidence-Based Path to Newborn Screening for Duchenne Muscular Dystrophy
Evidence-Based Path to Newborn Screening for Duchenne Muscular Dystrophy
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DOI：
10.1002/ana.23528
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发表时间：
2012-03-01
影响因子：
11.2
通讯作者：
Weiss, Robert B.
中科院分区：
文献类型：
--
作者：
Mendell, Jerry R.;Shilling, Chris;Weiss, Robert B.
目的：新生儿干血斑肌酸激酶（CK）水平升高与分娩过程有关。作为新生儿筛查的标志物，杜氏肌营养不良症（DMD）中的CK会导致假阳性检测。在这份报告中，我们介绍了一个2层系统，使用干血斑，首先评估CK与后续DMD基因testing.Methods：一个荧光分析的基础上，酶转磷酸腺苷二磷酸腺苷三磷酸被用来测量CK活性。初步研究使用30，547份匿名干血斑样本建立了新生儿CK的人群范围。突变分析使用从干血斑中提取的基因组DNA，然后进行全基因组扩增，使用多重连接依赖探针扩增评估DMD基因中的单/多外显子缺失/重复。结果：在37，649名新生男性受试者中，有6名发现DMD基因突变（所有外显子缺失），所有受试者的CK水平均>2，000 U/l。在3例CK >2，000 U/l的新生儿中，未发现DMD基因异常，我们确定了影响DYSF、SGCB和FKRP的肢带型肌营养不良基因突变。这种新生儿筛查的方法适合我们的医疗保健系统，最大限度地减少假阳性检测，并使用干血斑上的CK预定水平来预测DMD基因突变。神经网络2012;71：304-313
Objective: Creatine kinase (CK) levels are increased on dried blood spots in newborns related to the birthing process. As a marker for newborn screening, CK in Duchenne muscular dystrophy (DMD) results in false-positive testing. In this report, we introduce a 2-tier system using the dried blood spot to first assess CK with follow-up DMD gene testing.Methods: A fluorometric assay based upon the enzymatic transphosphorylation of adenosine diphosphate to adenosine triphosphate was used to measure CK activity. Preliminary studies established a population-based range of CK in newborns using 30,547 deidentified anonymous dried blood spot samples. Mutation analysis used genomic DNA extracted from the dried blood spot followed by whole genome amplification with assessment of single-/multiexon deletions/duplications in the DMD gene using multiplex ligation-dependent probe amplification.Results: DMD gene mutations (all exonic deletions) were found in 6 of 37,649 newborn male subjects, all of whom had CK levels >2,000U/l. In 3 newborns with CK >2,000U/l in whom DMD gene abnormalities were not found, we identified limb-girdle muscular dystrophy gene mutations affecting DYSF, SGCB, and FKRP.Interpretation: A 2-tier system of analysis for newborn screening for DMD has been established. This path for newborn screening fits our health care system, minimizes false-positive testing, and uses predetermined levels of CK on dried blood spots to predict DMD gene mutations. ANN NEUROL 2012;71:304-313