Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Am J Med Genet A. 2021 Nov;185(11):3294-3313. doi: 10.1002/ajmg.a.62434. Epub 2021 Aug 18.
Clinical characterization of a patient phenotype has been the quintessential approach for elucidating a differential diagnosis and a hypothesis to explore a potential clinical diagnosis. This has resulted in a language of medicine and a semantic ontology, with both specialty- and subspecialty-specific lexicons, that can be challenging to translate and interpret. There is no 'Rosetta Stone' of clinical medicine such as the genetic code that can assist translation and interpretation of the language of genetics. Nevertheless, the information content embodied within a clinical diagnosis can guide management, therapeutic intervention, and potentially prognostic outlook of disease enabling anticipatory guidance for patients and families. Clinical genomics is now established firmly in medical practice. The granularity and informative content of a personal genome is immense. Yet, we are limited in our utility of much of that personal genome information by the lack of functional characterization of the overwhelming majority of computationally annotated genes in the haploid human reference genome sequence. Whereas DNA and the genetic code have provided a 'Rosetta Stone' to translate genetic variant information, clinical medicine, and clinical genomics provide the context to understand human biology and disease. A path forward will integrate deep phenotyping, such as available in a clinical synopsis in the Online Mendelian Inheritance in Man (OMIM) entries, with personal genome analyses.
对患者表型的临床特征进行描述一直是阐明鉴别诊断和探索潜在临床诊断假说的主要方法。这导致了医学语言和语义本体的产生，其中包括专业和亚专业特定的词汇，这在翻译和解释上可能具有挑战性。医学领域没有像遗传学中的基因密码那样的“罗塞塔石碑”来协助翻译和解释医学语言。然而，临床诊断中所包含的信息内容可以指导疾病的管理、治疗干预，并且可能预测疾病的预后，从而为患者和家属提供前瞻性指导。临床基因组学现在已经在医学实践中得到了牢固的确立。个人基因组的粒度和信息量非常庞大。然而，由于我们缺乏对人类参考基因组序列中单倍体中绝大多数计算注释基因的功能特征的描述，我们对大部分个人基因组信息的利用受到了限制。尽管 DNA 和遗传密码为翻译遗传变异信息提供了“罗塞塔石碑”，但临床医学和临床基因组学为理解人类生物学和疾病提供了背景。未来的发展方向将是整合深度表型，例如在在线孟德尔遗传数据库（OMIM）条目中的临床综述中可用的表型，以及个人基因组分析。
