ABCMdb

PMID: 15579781

Tornovsky S, Crane A, Cosgrove KE, Hussain K, Lavie J, Heyman M, Nesher Y, Kuchinski N, Ben-Shushan E, Shatz O, Nahari E, Potikha T, Zangen D, Tenenbaum-Rakover Y, de Vries L, Argente J, Gracia R, Landau H, Eliakim A, Lindley K, Dunne MJ, Aguilar-Bryan L, Glaser B
Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity.
J Clin Endocrinol Metab. 2004 Dec;89(12):6224-34., [PubMed]

Sentences

No. Mutations Sentence Comment

72 ABCC8 p.Gly1342Glu Photolabeling and surface expression After an overnight incubation after electroporation, whole-cell photolabeling (25) and surface expression assays were performed as pre- TABLE1.Patientclinicaldata Patientno.Ethnicity Ageat diagnosis Responsive todiazoxide Responsive tooctreotide PancreatectomyHistologyElectrophysiologyFamilyhistoryMutationsidentified 1BengalBirthNoNoYesDiffuseKATPchannelopathyNo3992-9g3a (homozyg) 2BedouinBirthPartialPartialYesDiffuseNotdoneYesR836X(homozyg) 3IndiaBirthNoPartialYesDiffuseKATPchannelopathyNoG111R(homozyg) 4ArabBirthNoNoYesDiffuseNotdoneNoR1494W (homozyg) 5CaucasianBirthNoPartialYesDiffuseKATPchannelopathyNoG70Eand R1419H 6CaucasianBirthNoPartialYesDiffuseKATPchannelopathyNo2154ϩ3a3gand G1342E 7ArabBirthNoPartialYesDiffuseNotdoneNo1113insT (homozyg) 8ArabBirtha NoPartialYesDiffuseNotdoneYesP254L(homozyg) 9Bedouin2dPartialYesNoNotdoneCousinwithtransient neonatal hypoglycemia ϩ88g3t (homozyg) 10CaucasianBirthNoPartialYesDiffuseKATPchannelopathyYes(sister)2154ϩ3a3g (heterozyg) 11Caucasian3dNoNoYesDiffuseNotdoneNo-64c3g (heterozyg) 12AshkenaziJewishBirthNoPartialNoNotdoneNoNone 13MixedAshkenazi- SepharadicJewish 4-6monthsResponsiveNottestedNoNotdoneNoNone 14Caucasian4-6monthsNoNoYesDiffuseNodefectsNoNone 15CaucasianBirthYesNottestedNoNotdoneYesNone Homozyg,Homozygous;heterozyg,heterozygous. Login to comment 94 ABCC8 p.Gly1342Glu Patient 6 inherited this mutation on the maternal allele and was found to have a second mutation (G1342E) on the paternal allele (Table 2). Login to comment 98 ABCC8 p.Arg836* One, R836X, was identified in a proband from a Bedouin family and had previously been found in three families of Mexican origin (30). Login to comment 101 ABCC8 p.Gly111Arg ABCC8 p.Arg836* ABCC8 p.Gly1342Glu ABCC8 p.Gly70Glu ABCC8 -64 c3g Promoter gcc gcc ccc Promoter 11 gGc G70E 2 ccc ggg cac Missense 5 gAg G111R 3 gcc ggg atg Missense 3 Agg 2154 ϩ 3a3g Intron 15 agg tat ggc Splice-site 6, 10 tGt R836X 21 cag cga atc Nonsense 2 Tga 1113 ins T 27 ttt ttt gag Single-base insertion 7 ttt ttt Tga 3992-9 g3a Intron 32 cgc aag cgt Splice-site 1 aaA G1342E 33 caa ggg aag Missense 6 gAg R1419H 35 ctg cgc tca Missense 5 cAc R1494W 37 gcc cgg gcc Missense 4 Tgg KCBJ11 ϩ88 g3t Promoter gaa gtg agg Promoter 9 Ttg P254L Exon 1 gcc cCg ctg Missense 8 cTg a For each mutation, the upper line indicates the wt sequence, and the lower line indicates the mutant sequence. Login to comment 134 ABCC8 p.Arg836* Haplotype analysis of four families segregating the R836X mutation. Login to comment 164 ABCC8 p.Gly111Arg ABCC8 p.Arg836* ABCC8 p.Arg836* ABCC8 p.Gly70Glu When the mutations in ABCC8 (G70E, G111R, R836X, G1343E, R1419H, and R1494W) were expressed alone, all except R836X were photolabeled with the high-affinity sulfonylurea ligand [125 I]- azido-glibenclamide (data not shown). Login to comment 166 ABCC8 p.Arg836* The missense mutation, R836X, caused a truncation that resulted in loss of the binding site for glibenclamide. Login to comment 180 ABCC8 p.Gly111Arg ABCC8 p.Gly70Glu ABCC8 p.Gly70Glu In contrast, the mature form, which is indicative of channels trafficking at least to the Golgi, was present only in the G70E homozygote, in the G70E/R1419H compound heterozygote, and to a lesser extent, in G111R. Login to comment 185 ABCC8 p.Gly111Arg ABCC8 p.Gly70Glu ABCC8 p.Gly70Glu The first three SUR1 mutant channels, G70E homozygote, G70E/ R1419H compound heterozygote, and G111R, were expressed at the plasma membrane, albeit at much lower levels than the wild-type channel. Login to comment 188 ABCC8 p.Gly111Arg ABCC8 p.Gly70Glu We confirmed that channel activity of the G70E and G111R mutants was decreased when compared with wild-type controls. Login to comment 190 ABCC8 p.Gly70Glu Patient 5 was a compound heterozygote for mutations G70E and R1419H. Login to comment 222 ABCC8 p.Arg836* Three mutations (3992-9 g3a, R836X, and R1494W) were previously reported in other ethnic groups. Login to comment 236 ABCC8 p.Gly111Arg ABCC8 p.Gly70Glu ABCC8 p.Gly70Glu ABCC8 p.Pro254Leu COS cells coexpress wild-type (wt) KIR6.2 with SUR1 mutations (G70E, G70E/R1419H, G111R, G1343E, R1419H, and R1494W) or coexpress wt SUR1 with KIR6.2 mutation (P254L). Login to comment 242 ABCC8 p.Gly111Arg ABCC8 p.Arg836* ABCC8 p.Gly70Glu ABCC8 p.Pro254Leu Homozygous expression of G70E and G111R had reduced surface expression, whereas mutations R836X, G1343E, R1419H, R1494W, and P254L did not reach the plasma membrane at all, although they did associate with their respective wt partner as shown in Fig. 5A (lower panel). Login to comment 243 ABCC8 p.Gly70Glu ABCC8 p.Gly70Glu Compound heterozygous expression for mutation G70E/R1419H (4 ␮g/4 ␮g) showed reduced surface expression when compared with mutation G70E (8 ␮g) expressed alone. Login to comment 250 ABCC8 p.Gly111Arg ABCC8 p.Gly70Glu ABCC8 p.Gly70Glu Only G70E (8 ␮g), G111R (8 ␮g), and compound heterozygote G70E/R1419H (4 ␮g/4 ␮g) reconstituted with wt KIR6.2 (1 ␮g) show reduced efflux. Login to comment 280 ABCC8 p.Gly111Arg ABCC8 p.Gly70Glu In the current study, we describe two different missense mutations in the same domain, G70E and G111R. Login to comment