Hofstra R M, Osinga J, Buys C H
Department of Medical Genetics, University of Groningen, The Netherlands.
Eur J Hum Genet. 1997 Jul-Aug;5(4):180-5.
Hirschsprung disease is a congenital disorder clinically characterized by the absence of colonic ganglia and genetically by extensive heterogeneity. Genes involved include RET, GDNF, EDNRB and EDN3. Mutations of these genes may give dominant, recessive, or polygenic patterns of inheritance. In particular in the case of missense mutations, it is therefore far from easy to assess whether a given mutation will contribute to the phenotype. We discuss criteria for such an assessment and pay special attention to functional assays. The interpretation of mutations as contributing to a disease phenotype or as merely representing a rare polymorphism has direct clinical consequences. Hirschsprung disease with major and modifying sequence variants in a variety of genes might well serve as a model for the many complex disorders for which the search for genes involved has only just been initiated.
先天性巨结肠是一种先天性疾病，临床特征为结肠神经节缺失，遗传特征为广泛的异质性。相关基因包括RET、GDNF、EDNRB和EDN3。这些基因的突变可能呈现显性、隐性或多基因遗传模式。特别是在错义突变的情况下，因此很难评估给定的突变是否会导致表型。我们讨论了这种评估的标准，并特别关注功能测定。将突变解释为导致疾病表型或仅仅代表一种罕见的多态性具有直接的临床后果。在多种基因中存在主要和修饰序列变异的先天性巨结肠很可能作为许多复杂疾病的模型，而对于这些复杂疾病，寻找相关基因的工作才刚刚开始。
