Bareil C, Bergougnoux A
Laboratoire de Génétique Moléculaire, CHU de Montpellier, Montpellier, France.
Laboratoire de Génétique Moléculaire, CHU de Montpellier, Montpellier, France; EA7402 Laboratoire de Génétique de Maladies Rares, Institut Universitaire de Recherche Clinique, Université de Montpellier, Montpellier, France..
Arch Pediatr. 2020 Feb;27 Suppl 1:eS8-eS12. doi: 10.1016/S0929-693X(20)30044-0.
Pathogenic variants of the CFTR gene are responsible for a broad phenotypic spectrum characterized by malfunction of some exocrine tissues, with an autosomal recessive mode of inheritance. More than 2,000 variants, distributed throughout the CFTR gene, have been identified, with different effects on the gene and protein expression and function. Genotype-phenotype correlation studies have associated severe variants with a typical multi-organ form of cystic fibrosis, while mild variants are involved in monosymptomatic or adult-onset diseases, called CFTR-related disorders. However, the interpretation of rare variants remains challenging. This review presents an overview of the epidemiology of CFTR variants worldwide and in France and describes the functional classification. Finally, some frequent cystic fibrosis-causing and mild CFTR variants are used as example to depict the molecular pathology of the CFTR locus. Finally, we give the recommendations concerning nomenclature and classification that are useful for appropriate genetic counseling. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.
CFTR基因的致病变异导致了广泛的表型谱，其特征为一些外分泌组织功能异常，呈常染色体隐性遗传模式。已鉴定出分布于整个CFTR基因的2000多种变异，它们对基因以及蛋白质表达和功能有不同影响。基因型-表型相关性研究表明，严重变异与典型的多器官形式的囊性纤维化相关，而轻度变异则与单症状或成人发病疾病（称为CFTR相关疾病）有关。然而，对罕见变异的解读仍然具有挑战性。本综述概述了全球及法国CFTR变异的流行病学情况，并描述了功能分类。最后，以一些常见的导致囊性纤维化的变异和轻度CFTR变异为例，阐述CFTR位点的分子病理学。最后，我们给出了有关命名和分类的建议，这些建议有助于进行适当的遗传咨询。© 2020年法国儿科学会。由爱思唯尔马松出版社出版。保留所有权利。
