ABCMdb

PMID: 12531063

Lim M, Zeitlin PL
Therapeutic strategies to correct malfunction of CFTR.
Paediatr Respir Rev. 2001 Jun;2(2):159-64., [PubMed]

Sentences

No. Mutations Sentence Comment

60 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly551Ser ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Gly314Glu ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Type Genotype Phenotypea Defect Potential therapeutics Class I G542X PI No CFTR synthesis, aminoglycosides 621 + 1 G ࢐T No cell surface Cl- 3905insT transport W1282X R553X 1717-1 G ࢐ A Class II F508b PI Defective CFTR 4-PBA, flavonoids, N1303K trafficking and chemical chaperones, P574Hb processing xanthines A455Eb Class III G551D PI Defective channel flavonoids, milrinone G551S regulation, reduced or absent Cl-transport Class IV R117H PS Reduced Cl-transport 4-PBA, xanthines, R334W flavonoids G314E R347P F508b P574Hb ClassV 3849 + 10 kb C࢐T PS Reduced number of flavonoids, milrinone, 2789 + 5 G ࢐A normal CFTR proteins 4-PBA 3272 - 26 A ࢐ G Reduced Cl-transport A455Eb 3120+1 G࢐A 1811 + 1.6 kb A ࢐ G a PI indicates pancreatic insufficiency; PS indicates pancreatic sufficiency. Login to comment 63 ABCC7 p.Trp1282* At micromolar concentrations 4-PBA increases maturation of CFTR in IB3-1 cells (an immortalised CF cell line containing the mutations ࢞F508 and W1282X).14 This maturation was associated with the functional correction of the ࢞F508 transport defect, perhaps due to increased CFTR mRNA synthesis and/or more efficient folding/trafficking. Login to comment 71 ABCC7 p.Gly551Asp Therapies directed at Class III defects CFTR mutations such as G551D undergo normal trafficking to the plasma membrane, but are refractory to cAMP stimulation. Login to comment 75 ABCC7 p.Gly551Asp Genistein and certain related isoflavones (see below) directly activate chloride conductance in wild-type, G551D, and ࢞F508 CFTR. Login to comment