TY - JOUR T1 - Lung function and disease severity in cystic fibrosis patients heterozygous for <em>p.Arg117His</em> JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00056-2016 VL - 3 IS - 1 SP - 00056-2016 AU - Michal Shteinberg AU - Damian G. Downey AU - Diane Beattie AU - John McCaughan AU - Alastair Reid AU - Nili Stein AU - J. Stuart Elborn Y1 - 2017/01/01 UR - http://openres.ersjournals.com/content/3/1/00056-2016.abstract N2 - Expression of p.Arg117His cystic fibrosis (CF) transmembrane conductance regulator is influenced by a polythymidine (poly-T) tract and a thymidine–guanine (TG) repeat on intron 9, which vary in length and affect exon 10 skipping.We compared clinical characteristics and the rate of progression of lung disease of CF patients carrying the p.Arg117His mutation with different intron 9 varying sequences (poly-T) and mutation classes in trans.Data were collected from patients in Northern Ireland, UK, including diagnostic features, sweat chloride, nutritional status, sputum microbiology, CF-related complications and lung function. Poly-T and TG repeats were determined by PCR. Forced expiratory volume in 1 s (FEV1) decline was determined from linear regression of FEV1 measurements of patients over time.We identified 62 patients with p.Arg117His, 55 with a class I/II mutation in trans and six with p.Arg117His/p.Gly551Asp. 42 patients had 5T and 13 had 7T. All patients had 12 TG repeats. Patients with p.Arg117His-5T had greater lung function decline, sweat chloride concentrations, pancreatic insufficiency and prevalence of Pseudomonas aeruginosa infection compared with patients with p.Arg117His-7T.Lung function decline and disease severity in p.Arg117His is determined by the poly-T tract length and identity of the mutation in trans. Patients with p.Arg117His-5T and a second class I/II mutation have a severity similar to p.Phe508del homozygous patients, although lung function decline is delayed to an older age. There may be linkage disequilibrium between p.Arg117His and 12 TG repeats.p.Arg117His CFTR with 5T repeats is associated with accelerated lung function decline compared with p.Arg117His-7T http://ow.ly/yAdS308q3dn ER -