ABCMdb

ABCC8 p.His125Gln

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Publications

PMID: 16442101 [PubMed] Frelet A et al: "Insight in eukaryotic ABC transporter function by mutation analysis."

No. Sentence Comment

426 Shyng et al. [204] have reported that H125Q, N188S, F591L, T1139M, R1215Q and G1382S generated functional channels in the absence of ATP, indicating that the lack or reduction of KATP channel sensitivity to MgADP is a common molecular defect associated with the disease. Login to comment

PMID: 9648840 [PubMed] Shyng SL et al: "Functional analyses of novel mutations in the sulfonylurea receptor 1 associated with persistent hyperinsulinemic hypoglycemia of infancy."

No. Sentence Comment

2 We have studied the functional properties of novel SUR1 mutations identified in PHHI patients, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H. Login to comment
3 R1394H and F1388 SUR1, a previously identified PHHI mutation, resulted in no functional channels when coexpressed with Kir6.2 in COS cells, while H125Q, N188S, F591L, T1139M, R1215Q, and G1382S SUR1 generated functional channels in the absence of ATP. Login to comment
4 With the exception of N188S and H125Q, all mutants had reduced response to stimulation by MgADP. Login to comment
75 The positions of the seven newly identified SUR1 mutations that are associated with the disease PHHI are shown in Fig. 1, including H125Q, N188S, F591L, T1139M, R1215Q, G1382S, and R1394H on both SUR1 topology models. Login to comment
90 The level of activity of other channels follows the order of WT ~N188S ~T1139M > G1382S > H125Q > F591L > R1215Q. Login to comment
112 Compared with wild-type channels, H125Q had a slightlygreater response to diazoxide (P < 0.1, ANOVA), N188S hada response that is similar to the wild-type channel (NS, ANOVA), T1139M and G1382S mutant channels had slightly reduced responses, while F591L and R1215Q channels had severely reduced responses (P < 0.005 and 0.025, respectively, ANOVA) (Fig. 6). Login to comment
131 Another patient, compound heterozygous for the H125Q mutation and the F1388 mutation, had clinically mild disease. Login to comment
132 The mild disease is consistent with the functional data of the H125Q mutation. Login to comment
156 With the exception of N188S and H125Q, which formed channels that were indistinguishable from the wild-type in terms of regulation of the channel by nucleotides and diazoxide, all other mutants caused defects of various severity in the resulting channels. Login to comment
162 Although for some mutations ( F1388, H125Q, R1215Q, R1394H) the in vitro findings correlate well with the clinical observations, in other mutations there seems to be a discrepancy between in vitro and clinical observations. Login to comment
175 Five others (H125Q, N188S, F591L, T1139M, and R1215Q) are outside of the predicted nucleotide-binding folds. Login to comment
176 However, except for N188S and H125Q, these mutations all show some defects in regulation of the channel by MgADP or by diazoxide. Login to comment
185 Pancreatectomy BV N188S 3992-3 c-to-g <1 week Severe No Pancreatectomy CB H125Q F1388 1 year Mild No Pancreatectomy Q R1215Q 3992-9 g-to-a <1 week Severe Inadequate Pancreatectomy AO R1394H 3992-9 g-to-a < week Severe No Pancreatectomy BI F591L - <1 week Mild Yes Diazoxide BU G1382S - <1 week Severe ?? Login to comment

PMID: 9618169 [PubMed] Nestorowicz A et al: "Genetic heterogeneity in familial hyperinsulinism."

No. Sentence Comment

63 Mutations within the SUR1 gene Patient Exon or intron Nucleotide changea Codona predicted effect Domainb Restriction site change Frequency (%) HI chromosomes (n = 88) Segregation demonstrated Frequency 200 normal chromosomes A1 exon 2 221G→A R74Q Tm PstI 1 (1.1%) NA 0 B2d exon3 375C→G H125Q Tm DdeIc 1 (1.1%) NA 0 C3e exon 4 563A→G N188S Tm TspRI 1 (1.1%) yes 0 D4 exon 6 949delC 317fs/ter Tm Bsp1286I 1 (1.1%) yes 0 E5 exon 8 1216A→G N406D Tm XcmI 1 (1.1%) NA 0 F6f intron 10 1630+1G→T aberrant splicing Tm BsrI 2 (2.3%) yes 0 G7 exon 12 1773C→G F591L Tm BsoF1 1 (1.1%) no 0 H8 exon 13 1893delT 631fs/ter Tm BstNI 1 (1.1%) yes 0 F6f intron 15 2117-1G→A aberrant splicing NBF-1 PstI 1 (1.1%) yes 0 I9 exon 24 2860C→T Q954X - BstNI 1 (1.1%) yes 0 J10g exon 28 3416C→Th T1139M Tm NlaIII 1 (1.1%) yes 0 K11 exon 29 3644G→A R1215Q Tm NciI 1 (1.1%) yes 0 J10g intron 32 3992-9G→Ai aberrant splicing NBF-2 NciI 4 (4.5%) yes 0 C3e intron 32 3992-3C→G aberrant splicing NBF-2 AvaI 1 (1.1%) yes 0 L12 exon 34 4135G→C G1379R NBF-2 EagI 1 (1.1%) yes 0 M13 exon 34 4144G→A G1382S NBF-2 BglI 1 (1.1%) yes 0 B2d exon 34 4162delTTCi,j delF 1388 NBF-2 BseRI 1 (1.1%) yes 0 J10g exon 34 4181G→Ah R1394H NBF-2 DraIII 1 (1.1%) yes 0 N14 exon 35 4310G→Ai aberrant splicing NBF-2 MspI 1 (1.1%) yes 0 O15 exon 37 4525insCGGCTT insertion of AlaSer ft d 1508 NBF-2 PvuIIk 1 (1.1%) yes 0 after codon 1508 aNucleotide and codon positions are according to the full-length human SUR1 cDNA sequence incorporating the alternative splicedform of exon 17 (GenBank accession nos L78208 and L78216). Login to comment
200 A model for SUR1 (29) predicts that the remaining seven missense mutations (Arg74Gln, His125Gln, Asn188Ser, Asn406Asp, Phe591Leu, Thr1139Met, Arg1215Gln) are located either within transmembrane segments or are present on the extracellular or cytoplasmic loops connecting adjacent trans- membranehelices.Theidentificationofthesemissensemutations in HI patients provides a basis for further studies to elucidate the functions of these transmembrane domains in SUR1 and KATP channel activity. Login to comment
201 We have found that the His125Gln, Phe591Leu, Thr1139Met and Arg1215Gln mutations result in various reductions in the sensitivity of KATP channels to stimulation by MgADP in vitro (S.-L.Shyng et al., unpublished data). Login to comment
233 To detect the His125Gln mutation, which did not alter a restriction enzyme site, PCR-directed site-specific mutagenesis was used to incorporate a DdeI restriction site into products derived from wild-type alleles. Login to comment