Mekus et al. (1998) described a man who had recurrent bronchitis beginning at age 6 years, with a chronic cough and excessive sputum production that required 3 to 4 courses of antibiotics per year. At age 17 years, ... Mekus et al. (1998) described a man who had recurrent bronchitis beginning at age 6 years, with a chronic cough and excessive sputum production that required 3 to 4 courses of antibiotics per year. At age 17 years, he had severe pneumonia and was diagnosed as having cystic fibrosis (219700) because of elevated sweat chloride. Further investigation revealed subnormal lung function (forced expiratory volume in 1 second, 72% of predicted) and reduced fertility (below-normal sperm density and motility). However, no mutation was found in the CFTR gene (602421), and he and his healthy sister shared the same intragenic CFTR marker haplotypes. In addition, both sibs had a normal baseline nasal potential difference (NPD) and gluconate response, and intestinal current measurement (ICM) showed that a chloride secretory current was evoked by carbachol, suggesting that CFTR-mediated conductance in the respiratory and gastrointestinal tracts in both sibs was normal. The patient also had normal blood pressure, serum electrolytes, and plasma renin and aldosterone levels, both before and after the administration of furosemide.
In a man previously reported by Mekus et al. (1998) as having a cystic fibrosis (219700)-like phenotype but no mutations in the CFTR gene (602421), Azad et al. (2009) identified heterozygosity for a hyperactive mutation in the SCNN1A ... In a man previously reported by Mekus et al. (1998) as having a cystic fibrosis (219700)-like phenotype but no mutations in the CFTR gene (602421), Azad et al. (2009) identified heterozygosity for a hyperactive mutation in the SCNN1A gene (V114I; 600228.0006) that was not found in his healthy sister. Examination revealed an FEV1 that was 62% of expected, and the patient had a history of multiple episodes of reversible airway colonization with Staphylococcus aureus or Pseudomonas aeruginosa. He had an elevated sweat chloride but was pancreatic sufficient, and had no steatorrhea or other gastrointestinal symptoms. Although he had a low sperm count, he was the father of 2 children. He had a plasma renin of 1 ng/ml/h, plasma aldosterone of 101 pg/ml, and he had been hypertensive for several years (160/90). In addition, Azad et al. (2009) identified several rare SCNN1A polymorphisms with an increased incidence in patients with a cystic fibrosis-like phenotype and 1 or no CFTR mutations versus controls, including several patients with no CFTR mutation who were heterozygous for a hyperactive variant (W493R; 600228.0007). The authors suggested that there might be a polygenic mechanism of disease involving CFTR and SCNN1A in some patients. Mutesa et al. (2009) analyzed the CFTR gene in 60 unrelated Rwandan children who had CF-like symptoms and identified heterozygosity for a CFTR mutation in 5 patients (none were homozygous). Sequencing of the genes encoding the 3 subunits of the epithelial sodium channel (ENaC) revealed heterozygous mutations in SCNN1A and SCNN1B (600760) in 4 patients, respectively, whereas the remaining patient was heterozygous for a mutation in both SCNN1B and SCNN1G (600761). Among the patients who were negative for mutation in CFTR, only known polymorphisms were found in the ENaC genes. Mutesa et al. (2009) concluded that some cases of CF-like syndrome in Africa may be associated with mutations in CFTR and ENaC genes.