ABCMdb

PMID: 10021451

Zeitlin PL
Novel pharmacologic therapies for cystic fibrosis.
J Clin Invest. 1999 Feb;103(4):447-52., [PubMed]

Sentences

No. Mutations Sentence Comment

30 ABCC7 p.Gly551Asp Mutations, such as G551D, tend to be associated with a severe phenotype. Class IV mutations affect chloride conductance or channel gating and thus result in reduced chloride current. Login to comment 31 ABCC7 p.Arg117His ABCC7 p.Pro574His As might be expected, mutations in this class, such as R117H or P574H, are thought to confer a milder phenotype. Class V mutations reduce the level of normal CFTR protein by alterations in the promoter or by altering splicing. Login to comment 33 ABCC7 p.Ala455Glu Examples of Class V mutations include 3849 + 10kb C→T, A455E, and 5T. Login to comment 43 ABCC7 p.Arg117His ABCC7 p.Arg117His Perspective SERIES on cystic fibrosis James M. Wilson, Editor tion,R117H,occursinciswitheitherthe5Tor7Ttractvari- antinintron8.The5Talleleconfersapancreaticsufficient CF phenotype, whereas the 7T allele has been associated with male infertility caused by congenital bilateral absence ofthevasdeferens(CBAVD).Interestingly,womenwiththe R117H-7T allele tend to be asymptomatic. Login to comment 48 ABCC7 p.Trp1282* ABCC7 p.Arg553* This has been demonstrated for W1282X and R553X in vitro. Login to comment 49 ABCC7 p.Trp1282* Given that W1282X mRNA is unusually stable in certain patients (10), topical and inhaled gentamicin is under study in the United States and Israel (11, 12). Login to comment 116 ABCC7 p.Gly551Asp On the other hand, genistein alone induced a small chloride response in CF patients carrying one copy of the G551D mutation. Login to comment 117 ABCC7 p.Gly551Asp G551D is a Class III mutation that is synthesized, resides in the plasma membrane but is not activated with isoproterenol. Login to comment 118 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp The ability of genistein to activate G551D in the intestine of the G551D CF mouse has also been observed (47). Login to comment 121 ABCC7 p.Gly551Asp G551D is a common mutation associated with pancreatic insufficiency and the severe phenotype. Login to comment 122 ABCC7 p.Gly551Asp G551D CFTR does not conduct chloride in response to elevated cAMP but is resident in the plasma membrane. Login to comment 123 ABCC7 p.Gly551Asp Genistein and related compounds are the first chemicals ever shown to stimulate G551D chloride conductance in vitro. Login to comment 125 ABCC7 p.Gly551Ser ABCC7 p.Gly1244Glu ABCC7 p.Gly1349Asp ABCC7 p.Ser1255Pro These mutants sustain a reduced response to ATP-examples include S1255P, G551S, G1244E, and G1349D. Login to comment 128 ABCC7 p.Arg117His ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Gly314Glu Class IV mutants such as R117H, G314E, R334W, and R347P are associated with normal PKA-dependent phosphorylation and ATP binding. Login to comment 131 ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Arg347Pro R347P affects the rate of chloride flow, whereas R117H and P574H reduce the channel open time. Login to comment 133 ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Ala455Glu ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro Class IV mutations such as R117H, R334W, R347P, A455E, and P574H are associated with a pancreatic sufficient phenotype or late onset pancreatic insufficiency. Login to comment 141 ABCC7 p.Arg117His A second murine model, the R117H mouse, expresses a mutant which is found in the cell surface in humans. Login to comment 204 ABCC7 p.Trp1282* Similar levels of mRNA from the W1282X and the delta F508 cystic fibrosis alleles, in nasal epithelial cells. J. Clin. Invest. 93:1502-1507. 11. Login to comment 339 ABCC7 p.Gly551Asp Genistein stimulates chloride secretion in normal volunteers and CF patients with a G551D mutation. Login to comment 345 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp Effect of IBMX and alkaline phosphatase inhibitors on Cl-secretion in G551D cystic fibrosis mutant mice. Login to comment 349 ABCC7 p.Arg553* ABCC7 p.Trp1316* Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis. Login to comment