ABCMdb

PMID: 26474553

Lenherr N, Lura M, Trachsel D, Latzin P, Hammer J
Ivacaftor in a young boy with the rare gating mutation S549R--use of lung clearance index to track progress: a case report.
BMC Pulm Med. 2015 Oct 16;15:123. doi: 10.1186/s12890-015-0120-1., [PubMed]

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No. Mutations Sentence Comment

0 ABCC7 p.Ser549Arg CASE REPORT Open Access Ivacaftor in a young boy with the rare gating mutation S549R - use of lung clearance index to track progress: a case report Nina Lenherrߤ , Marco Lur&#e0;ߤ , Daniel Trachsel, Philipp Latzin and Juerg Hammer* Abstract Background: Ivacaftor acts as a potentiator of the cystic fibrosis transmembrane conductance regulator (CFTR) and increases the transepithelial chloride transport of CFTR in 9 of 10 known gating mutations causing cystic fibrosis. Login to comment 1 ABCC7 p.Ser549Arg S549R is a rare gating mutation considered to be less sensitive to potentiators than all other gating mutations. Login to comment 2 ABCC7 p.Ser549Arg Case presentation: We report our first experience with ivacaftor in an 8-year-old boy with the rare S549R gating mutation. Login to comment 5 ABCC7 p.Arg117His ABCC7 p.Ser549Arg Keywords: Cystic fibrosis, Ivacaftor, S549R, Gating mutation, N2MBW, LCI Background Ivacaftor acts as a potentiator of the cystic fibrosis transmembrane conductance regulator (CFTR) and increases the transepithelial chloride (Cl- ) transport of CFTR in 9 of 10 known gating mutations and in R117H mutation (class IV) causing cystic fibrosis. Login to comment 6 ABCC7 p.Gly551Asp Ivacaftor has been approved in 2012 by the US Food and Drug Administration (FDA) for G551D, the most common gating mutation, after improvements in lung function and lowering of sweat chloride levels had been demonstrated in clinical trials [1]. Login to comment 7 ABCC7 p.Ser549Arg In 2014 the approval was extended for 8 additional gating mutations, including S549R. Login to comment 8 ABCC7 p.Ser549Arg S549R is a rare gating mutation (41 described patients in CFTR2 [2]) primarily described in the Bedouin population of the United Arab Emirates, in Saudi Arabia and in North Africa. Login to comment 9 ABCC7 p.Ser549Arg The clinical phenotype seen with the homozygous S549R mutation is generally severe and similar to homozygous deltaF508 mutation [3, 4]. Login to comment 16 ABCC7 p.Ser549Arg We report our first experience with ivacaftor and the usefulness of LCI in a young Swiss patient with the S549R mutation to demonstrate improvements in lung function in response to this therapy when FEV1 is within normal limits. Login to comment 19 ABCC7 p.Ser549Arg Lenherr et al. BMC Pulmonary Medicine (2015) 15:123 DOI 10.1186/s12890-015-0120- Case presentation Case report An 8-year-old boy with S549R/1717-1G > A genotype was started on ivacaftor (150 mg b.i.d.) on compassionate use. Login to comment 32 ABCC7 p.Ser549Arg However, the weakest drug effect was described for the S549R mutation [5]. Login to comment 33 ABCC7 p.Ser549Arg S549R was initially considered a class II mutation leading to defective CFTR protein processing [12]. Login to comment 34 ABCC7 p.Ser549Arg Recent electrophysiological studies using Fischer rat thyroid cells have suggested the presence of a predominant gating defect besides a mild processing defect of CFTR in S549R [5]. Login to comment 36 ABCC7 p.Ser549Arg Against this background, the impressive clinical and functional improvement in our patient with the S549R mutation was better than expected. Login to comment 37 ABCC7 p.Ser549Arg These results are in line with a recently published clinical trial study including four patients with S549R mutation [6]. Login to comment 45 ABCC7 p.Ser549Arg Conclusion This report provides anecdotal evidence of benefit of ivacafor in S549R mutation. Login to comment 58 ABCC7 p.Gly551Asp Received: 28 April 2015 Accepted: 8 October 2015 References 1. Davies JC, Wainwright CE, Canny GJ, Chilvers MA, Howenstine MS, Munck A, et al. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Login to comment 78 ABCC7 p.Gly551Asp De Boeck K, Munck A, Walker S, Faro A, Hiatt P, Gilmartin G, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. Login to comment 111 ABCC7 p.Gly551Asp Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D-CFTR mutation and preserved spirometry: a randomised controlled trial. Login to comment