University of Exeter Medical School, Institute of Biomedical and Clinical Science, Royal Devon and Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK.
Medical Research Council Human Genetics Unit, The Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Nat Rev Genet. 2018 May;19(5):253-268. doi: 10.1038/nrg.2017.116. Epub 2018 Feb 5.
The majority of rare diseases affect children, most of whom have an underlying genetic cause for their condition. However, making a molecular diagnosis with current technologies and knowledge is often still a challenge. Paediatric genomics is an immature but rapidly evolving field that tackles this issue by incorporating next-generation sequencing technologies, especially whole-exome sequencing and whole-genome sequencing, into research and clinical workflows. This complex multidisciplinary approach, coupled with the increasing availability of population genetic variation data, has already resulted in an increased discovery rate of causative genes and in improved diagnosis of rare paediatric disease. Importantly, for affected families, a better understanding of the genetic basis of rare disease translates to more accurate prognosis, management, surveillance and genetic advice; stimulates research into new therapies; and enables provision of better support.
大多数罕见病影响儿童，其中大多数患者的疾病都有潜在的遗传原因。然而，利用现有技术和知识做出分子诊断通常仍然是一个挑战。儿科基因组学是一个不成熟但快速发展的领域，它通过将下一代测序技术，特别是外显子组测序和全基因组测序，纳入研究和临床工作流程，来解决这个问题。这种复杂的多学科方法，加上人群遗传变异数据的可用性不断增加，已经导致致病基因的发现率提高，并改善了罕见儿科疾病的诊断。重要的是，对于受影响的家庭来说，对罕见疾病遗传基础的更好理解可转化为更准确的预后、管理、监测和遗传咨询；促进新疗法的研究；并提供更好的支持。
