The "mild" gene variant, p.Arg117His in cystic fibrosis (CF) results in highly variable phenotypes ranging from male infertility to severe lung disease.
Patients with two identified CFTR mutations which include the R117H/7T anomaly should be followed up routinely as they remain susceptible to severe lung disease.
The 5T allele in intron 8 (IVS8) causes abnormal splicing in the CFTR gene, and is associated with lung disease when it occurs in cis with a missense mutation in the CFTR gene, R117H.
Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations.
Although several mutations are known to be associated with less severe pancreatic disease, our findings demonstrate a correlation between the A455E mutation and mild pulmonary disease.
Both G551D, a mutation that causes severe lung disease, and A455E, a mutation associated with mild lung disease, altered but did not abolish CFTR's function as a chloride channel in Xenopus oocytes.
Both G551D, a mutation that causes severe lung disease, and A455E, a mutation associated with mild lung disease, altered but did not abolish CFTR's function as a chloride channel in Xenopus oocytes.
To investigate the role of p.Arg75Gln in idiopathic chronic pancreatitis (ICP), we performed genotyping of the CFTR gene in 880 patients with ICP, 198 patients with idiopathic bronchiectasis (IB), 74 patients with classical cystic fibrosis (CF), 48 patients with congenital bilateral absence of the vas deferens (CBAVD) and 148 healthy controls. p.Arg75Gln variant was identified in 3.3% (29/880) of patients with ICP, 3.3% (9/272) patients with a pulmonary disease, 2.1% (1/48) of patients with CBAVD and 4.7% (7/148) of healthy controls.
These data suggest that the 5T polythymidine tract sequence on specific haplotype backgrounds (TG12 and M470V) may cause a low level of full-length functional CFTR protein and CF-like lung disease.
We classify N1303K as a "severe" mutation with respect to the pancreas, but can find no correlation between this mutation, in either the homozygous or heterozygous state, and the severity of lung disease.
We classify N1303K as a "severe" mutation with respect to the pancreas, but can find no correlation between this mutation, in either the homozygous or heterozygous state, and the severity of lung disease.