Program in Vertebrate Developmental Biology, Departments of Pediatrics and Genetics, Yale University School of Medicine, New Haven, CT.
Department of Epidemiology, Human Genetics and Environmental Sciences and Human Genetics Center, UTHealth School of Public Health, Houston, TX.
Birth Defects Res. 2017 Jan 30;109(2):180-185. doi: 10.1002/bdra.23590. Epub 2017 Jan 27.
Birth defects are the leading cause of infant death in the United States and among the top causes of pediatric death and hospitalization. Despite the devastating impact of birth defects, we understand little of their etiology impeding progress towards treatment and prevention. Moreover, while surgical interventions have improved survival for many children to beyond their first year, our inability to accurately predict, diagnose and treat the common sequelae of birth defects leaves the economic, social and public health burden of birth defects unacceptably high. An estimated one-third of all pediatric hospital beds are occupied by a child with a genetic diagnosis, and emerging genomic sequencing technologies provide an unprecedented opportunity to identify the genetic variants, including those that cause birth defects. It is essential that we leverage these advances to enhance our understanding of birth defects. Such an effort will lead to new avenues for treatment and provide benefits to families, including improved understanding of the cause of a child's condition and the risks to any future children. Understanding the genetics of human birth defects presents many challenges, some shared with other pathologies and some unique. This White Paper outlines the need for a birth defect genomics initiative, the challenges to overcome, and suggested solutions. Ultimately, we conclude that understanding birth defects must be a trans-NIH effort and involve the development of a new type of interdisciplinary team comprised of clinicians, geneticists, genomicists, epidemiologists, biostatisticians and basic cellular and developmental biologists working together in all aspects of the enterprise. Birth Defects Research 109:180-185, 2017. © 2017 Wiley Periodicals, Inc.
出生缺陷是美国婴儿死亡的主要原因，也是导致儿科死亡和住院的主要原因之一。尽管出生缺陷具有破坏性影响，但我们对其病因知之甚少，这阻碍了治疗和预防工作的进展。此外，尽管手术干预已经提高了许多儿童的生存率，使他们能够活过一岁，但我们无法准确预测、诊断和治疗出生缺陷的常见后遗症，这使得出生缺陷的经济、社会和公共卫生负担仍然过高。据估计，所有儿科病床中有三分之一被患有遗传诊断的儿童占据，新兴的基因组测序技术为识别遗传变异提供了前所未有的机会，包括导致出生缺陷的遗传变异。我们必须利用这些进展来增强对出生缺陷的认识，这一点至关重要。这一努力将为治疗开辟新途径，并为家庭带来益处，包括更好地了解孩子病情的原因以及对任何未来孩子的风险。了解人类出生缺陷的遗传学存在许多挑战，其中一些与其他病理学共享，而另一些则是独特的。本白皮书概述了开展出生缺陷基因组学计划的必要性、需要克服的挑战以及建议的解决方案。最终，我们得出结论，必须开展一项跨 NIH 的理解出生缺陷的工作，并涉及组建一种新型跨学科团队，由临床医生、遗传学家、基因组学家、流行病学家、生物统计学家以及基础细胞和发育生物学家共同组成，从各个方面开展工作。出生缺陷研究 109:180-185, 2017. © 2017 Wiley Periodicals, Inc.
