1. The Epithelial Sodium Channel Is a Modifier of the Long-Term Nonprogressive Phenotype Associated with F508del CFTR Mutations
- Author
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Agrawal, Pankaj B, Wang, Ruobing, Li, Hongmei Lisa, Schmitz-Abe, Klaus, Simone-Roach, Chantelle, Chen, Jingxin, Shi, Jiahai, Louie, Tin, Sheng, Shaohu, Towne, Meghan C, Brainson, Christine F, Matthay, Michael A, Kim, Carla F, Bamshad, Michael, Emond, Mary J, Gerard, Norma P, Kleyman, Thomas R, and Gerard, Craig
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Human Genome ,Orphan Drug ,Cystic Fibrosis ,Rare Diseases ,Pediatric ,Lung ,2.1 Biological and endogenous factors ,Aetiology ,Congenital ,Amino Acid Sequence ,Animals ,Cystic Fibrosis Transmembrane Conductance Regulator ,Epithelial Sodium Channels ,Female ,Humans ,Male ,Sequence Deletion ,Xenopus ,Xenopus laevis ,cystic fibrosis ,ENaC ,epithelial sodium channel ,genetic modifier ,SCNN1D ,Cardiorespiratory Medicine and Haematology ,Respiratory System ,Biochemistry and cell biology ,Cardiovascular medicine and haematology - Abstract
Cystic fibrosis (CF) remains the most lethal genetic disease in the Caucasian population. However, there is great variability in clinical phenotypes and survival times, even among patients harboring the same genotype. We identified five patients with CF and a homozygous F508del mutation in the CFTR gene who were in their fifth or sixth decade of life and had shown minimal changes in lung function over a longitudinal period of more than 20 years. Because of the rarity of this long-term nonprogressive phenotype, we hypothesized these individuals may carry rare genetic variants in modifier genes that ameliorate disease severity. Individuals at the extremes of survival time and lung-function trajectory underwent whole-exome sequencing, and the sequencing data were filtered to include rare missense, stopgain, indel, and splicing variants present with a mean allele frequency of
- Published
- 2017