Departments of Medicine and Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
Can J Cardiol. 2013 Jan;29(1):18-22. doi: 10.1016/j.cjca.2012.10.010. Epub 2012 Nov 28.
Monogenic diseases have a distinctive familial inheritance that follows Mendel's laws, showing patterns like dominant, recessive, or X-linked. There are > 7000 monogenic diseases curated in databases, and together they account for up to 10% of all illnesses encountered in the emergency room or clinic. Despite the rarity of individual monogenic conditions, mapping their causative genes and mutations is important for several reasons. First, knowing the causative gene and mutation could provide actionable information for genetic counselling. Sometimes, knowing the gene and mutation allows for early diagnosis in affected families, which is important if there is an evidence-based intervention. Second, the implication of a mutant gene as being causative for a clinical phenotype provides strong evidence of the importance of the gene product in a cellular or biochemical pathway. Discovery of new molecular pathways in families with rare diseases can serve as the first step toward developing rational therapies to help not only affected families, but also patients with less extreme, nongenetic forms of the same condition. For instance, the study of rare patients with familial hypercholesterolemia helped in developing statin drugs, initially as a treatment for familial hypercholesterolemia but now a widely used therapy to reduce low-density lipoprotein cholesterol and cardiovascular disease risk.
单基因疾病具有独特的家族遗传模式，遵循孟德尔定律，表现为显性、隐性或 X 连锁等形式。在数据库中已经有超过 7000 种单基因疾病被收录，它们总共占急诊室或诊所遇到的所有疾病的 10%。尽管个别单基因疾病较为罕见，但确定其致病基因和突变具有重要意义。首先，了解致病基因和突变可以为遗传咨询提供可行的信息。有时，在受影响的家族中进行早期诊断，如果有循证干预措施，这是很重要的。其次，突变基因与临床表型的因果关系提供了强有力的证据，证明该基因产物在细胞或生化途径中的重要性。在罕见疾病的家族中发现新的分子途径，可以作为开发合理治疗方法的第一步，不仅可以帮助受影响的家庭，还可以帮助患有同一疾病非遗传形式的患者。例如，对家族性高胆固醇血症的罕见患者的研究有助于开发他汀类药物，最初是作为家族性高胆固醇血症的治疗方法，但现在已广泛用于降低低密度脂蛋白胆固醇和心血管疾病风险。
