Developmental delay affects 1-2% of children worldwide. Symptoms often associated with developmental delay include impaired cognition, failure to meet developmental milestones, craniofacial and skeletal abnormalities, autism, and seizures. These disabilities can pose major medical, financial and psychological challenges.
在许多情况下，对于患有发育迟缓的儿童的具体诊断难以捉摸，缺乏诊断是患者及其家人的重大困难。不准确或不可用的诊断可能会导致多年的昂贵，侵入性和徒劳的测试使治疗决策复杂化，并可能导致焦虑和情绪困扰。此外，不知道具体发展延迟的原因会减慢研究对改善治疗或教育选择的速度。
为了结束针对发育迟缓的儿童的诊断奥德赛，我们采用了大规模的DNA测序来确定与发育障碍有关的特定遗传变异。作为NHGRI资助的临床测序探索性研究联盟的一部分，我们于2013年开始将受影响的儿童纳入我们的研究。到目前为止，我们已经对371名儿童进行了延迟，我们发现了遗传学原因，因此有助于做出遗传原因，因此有助于更精确和确定的临床诊断 - 分别为27％。
We also enrolled biological parents when available to facilitate the identification of “de novo” – i.e., present in a child but absent from his/her parents – genetic variants, as these are known to be enriched among variants that cause developmental disabilities.
通过测序影响孩子和他们的父母，，，，we were able in many cases to more efficiently identify the pathogenic variant relevant to their symptoms. In addition, by efficiently revealing relatively short lists of candidate de novo variants, trio sequencing also can greatly improve discovery of novel disease contributions.
That said, through retrospective analysis of proband genetic variants in the absence of parental sequence information, we were able to show that completing sequencing for only the child will often still yield a diagnosis, but will on average require more time and analytical effort when compared to the analysis of a trio.
重新分析的成功是由临床医生和科学家的数据共享的驱动和依赖，他们也在对发育迟缓的患者进行测序。
通过我们的研究，我们观察到，当近亲患有神经系统疾病时，在受影响的儿童中找到一种致病性变异更具挑战性。这一发现表明，这种“多重”家族中的潜在遗传学比“单纯形”家族更复杂，更难解释，并且这种区别在致病变异发现方面影响了成功率。
我们还证明，随着受影响儿童的数据的重新分析，没有最初发现的因果遗传发现通常会导致新发现，从而大大提高整体产量。重新分析的成功是由临床医生和科学家的数据共享的驱动和依赖，他们也在对发育迟缓的患者进行测序。
我们的数据强调了整个基因组测序作为发育障碍患者的有效的第一选择诊断工具的价值。此外，这种测序，尤其是作为概率和父母的三重奏，将提高临床和研究进展，并减少继续影响许多儿童及其家人的诊断奥德赛的数量和长度。
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