Bergougnoux Anne, Lopez Maureen, Girodon Emmanuelle
Molecular Genetics Laboratory, CHU Montpellier, EA7402 University of Montpellier, 34093 Montpellier CEDEX 5, France;
Molecular Genetics Laboratory, Cochin Hospital, APHP. Centre, University of Paris, 75014 Paris, France;
Int J Neonatal Screen. 2020 Mar 21;6(1):23. doi: 10.3390/ijns6010023. eCollection 2020 Mar.
There has been considerable progress in the implementation of newborn screening (NBS) programs for cystic fibrosis (CF), with DNA analysis being part of an increasing number of strategies. Thanks to advances in genomic sequencing technologies, -extended genetic analysis (EGA) by sequencing its coding regions has become affordable and has already been included as part of a limited number of core NBS programs, to the benefit of admixed populations. Based on results analysis of existing programs, the values and challenges of EGA are reviewed in the perspective of its implementation on a larger scale. Sensitivity would be increased at best by using EGA as a second tier, but this could be at the expense of positive predictive value, which improves, however, if EGA is applied after testing a variant panel. The increased detection of babies with an inconclusive diagnosis has proved to be a major drawback in programs using EGA. The lack of knowledge on pathogenicity and penetrance associated with numerous variants hinders the introduction of EGA as a second tier, but EGA with filtering for all known CF variants with full penetrance could be a solution. The issue of incomplete knowledge is a real challenge in terms of the implemention of NBS extended to many genetic diseases.
囊性纤维化（CF）新生儿筛查（NBS）项目的实施取得了显著进展，DNA分析在越来越多的筛查策略中发挥作用。得益于基因组测序技术的进步，通过对编码区域进行测序的扩展基因分析（EGA）变得经济可行，并且已经被纳入少数核心NBS项目，这对混合人群有益。基于现有项目的结果分析，从更大规模实施的角度审视了EGA的价值和挑战。将EGA用作第二层检测时，敏感性最多只能提高，但这可能会牺牲阳性预测值，不过，如果在检测一组变异后应用EGA，阳性预测值会有所改善。在使用EGA的项目中，对诊断不明确婴儿的检测增加已被证明是一个主要缺点。与众多变异相关的致病性和外显率方面的知识匮乏阻碍了将EGA用作第二层检测，但对所有已知具有完全外显率的CF变异进行过滤的EGA可能是一种解决方案。在将NBS扩展到多种遗传疾病的实施方面，知识不完整的问题是一个真正的挑战。
