ABCMdb

PMID: 21671388

Uitto J, Bercovitch L, Terry SF, Terry PF
Pseudoxanthoma elasticum: progress in diagnostics and research towards treatment : Summary of the 2010 PXE International Research Meeting.
Am J Med Genet A. 2011 Jul;155A(7):1517-26. doi: 10.1002/ajmg.a.34067. Epub 2011 Jun 10., [PubMed]

Sentences

No. Mutations Sentence Comment

25 ABCC6 p.Arg1141* ABCC6 p.Arg1268Gln There are recent suggestions, however, that certain mutations in ABCC6 may bestatistically associatedwithinvolvementofspecifictargetorgans, such as the p.R1268Q mutation being associated with early onset of angioidstreaks[Satoetal.,2009;Lietal.,2011a],andthestopcodon mutation p.R1141X possibly predisposing the individuals to car- diovascularinvolvementindependentofhyperlipidemiainpatients with PXE [K€obl€os et al., 2010; Pisciotta et al., 2010]. Login to comment 169 ABCC6 p.Arg1314Trp In this meeting, it was reported that selected mutant ABCC6 proteins harboring missense mutations, such as p.R1314W, showed initially a problem in intracellular trafficking leading to incorrect localization, as determined in vitro in the Sf9 and MDCKII cell systems and in an in vivo liver-targeted system in mouse [Pomozi et al., 2010]. Login to comment 170 ABCC6 p.Arg1314Trp However, exposure to sodium 4-phenylbutyrate restored the plasma membrane targeting with restoration of substantial transport activity. These data suggest, therefore, that intracellular trafficking of functionally active but misdirected ABCC6 mutants, such a p.R1314W, can be pharmacologically corrected by sodium 4-phenylbutyrate. Login to comment