ABCMdb

PMID: 19176844

Tummler B, Stanke F, Bronsveld I, Veeze H, Ballmann M
Transient correction of the basic defect in sweat glands in an individual with cystic fibrosis carrying the complex CFTR allele F508del-R553Q.
Thorax. 2009 Feb;64(2):179-80., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Arg553Gln ABCC7 p.Arg553Gln Transient correction of the basic defect in sweat glands in an individual with cystic fibrosis carrying the complex CFTR allele F508del-R553Q B Tu¨mmler,1,2 F Stanke,1 I Bronsveld,3 H Veeze,4 M Ballmann2 1 Klinische Forschergruppe, Medizinische Hochschule Hannover, Hannover, Germany; 2 Abteilung fu¨r Pa¨diatrische Pneumologie und Neonatologie, Medizinische Hochschule Hannover, Hannover, Germany; 3 Department of Pulmonology and Tuberculosis, Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands; 4 Stichting Diabeter, Rotterdam, The Netherlands Correspondence to: Dr B Tu¨mmler, Klinische Forschergruppe, OE 6710, Medizinische Hochschule Hannover, Carl-Neuberg-Str 1, D-30625 Hannover, Germany; tuemmler.burkhard@ mh-hannover.de Received 17 January 2008 Accepted 2 June 2008 ABSTRACT The molecular pathology of mutant F508del CFTR is partially corrected in vitro by the secondary amino acid substitution R553Q in the ABC signature motif. Login to comment 1 ABCC7 p.Arg553* ABCC7 p.Arg553Gln An individual with the CFTR genotype R553X/F508del-R553Q showed the typical symptoms and electrophysiological anomalies of cystic fibrosis in the airways and intestine. Login to comment 2 ABCC7 p.Arg553Gln Sweat chloride concentrations were normal early in life, but were later raised into the range that is diagnostic for cystic fibrosis, suggesting that R553Q could temporarily correct the basic defect in sweat glands. Login to comment 3 ABCC7 p.Arg553Gln R553Q caused a delay in diagnosis because of false negative sweat tests but was not a disease reverting suppressor mutation as had been inferred from cellular models. Login to comment 5 ABCC7 p.Arg553Gln ABCC7 p.Arg553Gln ABCC7 p.Arg553Gln ABCC7 p.Arg553Gln Here we report on the 30 year course of a basic defect and disease in an individual with cystic fibrosis (CF) who was compound heterozygous for the cystic fibrosis transmembrane conductance regulator (CFTR) mutations R553X1 and the complex allele F508del-R553Q.2 The amino acid substitution R553Q resides within the ABC signature motif of CFTR.3 R553Q has been shown in heterologous model systems to partially correct the defective processing and anomalous ion channel gating of mutant F508del CFTR.4 Hence R553Q has been classified as a disease reverting suppressor mutation. Login to comment 8 ABCC7 p.Arg553* The R553X/F508del- R5553Q index case showed a strong increase in sweat electrolytes from infancy to adulthood. Login to comment 23 ABCC7 p.Arg553* ABCC7 p.Arg553* ABCC7 p.Arg553Gln ABCC7 p.Arg553Gln The clinical characteristics of the R553X/F508del-R553Q subject were similar to those of R553X/F508del compound heterozygotes.2 Moreover, even in the sweat gland, the basic defect was corrected only early in life, but faded over the years, indicating that aging mechanisms abolished the rescue by R553Q in the morphologically inconspicuous tissue. Login to comment 24 ABCC7 p.Arg553Gln In summary, R553Q rescued the molecular pathology of F508del CFTR in a cellular model, but it was not a disease reverting suppressor mutation in the affected individual. Login to comment