Wilschanski Michael
Pediatric Gastroenterology Unit, Division of Pediatrics, Hadassah University Hospitals, Hebrew University, POB 24035, Jerusalem, Israel.
Curr Gastroenterol Rep. 2008 Jun;10(3):316-23. doi: 10.1007/s11894-008-0062-3.
This review focuses on the pathobiology of the gastrointestinal and hepatic manifestations of cystic fibrosis (CF) disease in relation to their genetic basis in mutations of the CF transmembrane conductance regulator (CFTR) gene. It reviews the nature of the CFTR protein, a categorization of the types of gene mutations underlying CF's various manifestations, and the ways in which absent or reduced CFTR produces various functional abnormalities in the different organs affected by CF. Subsequently, the particular organ-related clinical manifestations of CF directly associated with loss of CFTR function are addressed. Thereafter, the review discusses some of the complexities of the genotype-phenotype relationships related to milder mutations or complex genetic disorders in which CFTR abnormalities interact with other genetic and environmental factors, and the potential diagnostic roles of sweat testing or other electrophysiologic testing. This discussion examines secondary gastrointestinal manifestations of CF and the particular cases of diseases that may be related to abnormalities of CFTR.
本综述聚焦于囊性纤维化(CF)疾病的胃肠道和肝脏表现的病理生物学,及其与CF跨膜传导调节因子(CFTR)基因突变的遗传基础的关系。它回顾了CFTR蛋白的性质、CF各种表现背后基因突变类型的分类,以及CFTR缺失或减少在受CF影响的不同器官中产生各种功能异常的方式。随后,阐述了与CFTR功能丧失直接相关的CF特定器官相关临床表现。此后,该综述讨论了与较轻突变或复杂遗传疾病相关的基因型-表型关系的一些复杂性,其中CFTR异常与其他遗传和环境因素相互作用,以及汗液检测或其他电生理检测的潜在诊断作用。本讨论审视了CF的继发性胃肠道表现以及可能与CFTR异常相关的特定疾病病例。