Transient correction of the basic defect in sweat glands in an individual with cystic fibrosis carrying the complex CFTR allele F508del-R553Q.
The molecular pathology of mutant F508del CFTR is partially corrected in vitro by the secondary amino acid substitution R553Q in the ABC signature motif. An individual with the CFTR genotype R553X/F508del-R553Q showed the typical symptoms and electrophysiological anomalies of cystic fibrosis in the airways and intestine. 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. 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.
Tümmler
B
B
Klinische Forschergruppe, OE 6710, Medizinische Hochschule Hannover, Carl-Neuberg-Str 1, D-30625 Hannover, Germany. tuemmler.burkhard@mh-hannover.de
Stanke
F
F
Bronsveld
I
I
Veeze
H
H
Ballmann
M
M
D000328:Adult; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005188:False Negative Reactions; D005260:Female; D016153:Genes, Suppressor / Q000502:physiology; D006801:Humans; D009154:Mutation / Q000235:genetics*; D012965:Sodium Chloride / Q000378:metabolism; D013542:Sweat / Q000737:chemistry; D013543:Sweat Gland Diseases / Q000235:genetics*
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012965:Sodium Chloride