ABCMdb

ABCC8 p.Arg1436Gln

None has been submitted yet.

Publications

PMID: 17466004 [PubMed] Muzyamba M et al: "Complex ABCC8 DNA variations in congenital hyperinsulinism: lessons from functional studies."

No. Sentence Comment

3 Results The first case had diffuse disease and was homozygous for the mutations D1193V and R1436Q in SUR1. Login to comment
4 Channel complexes containing the D1193V mutant were delivered to the plasma membrane and were functional and those containing R1436Q were also present at the plasma membrane but were nonfunctional. Login to comment
5 Combining the two mutations (SUR1D1193V/R1436Q) led to intracellular retention of the channel complex. Login to comment
30 There is also a notation based on a potential splice variant of 1582 amino acids in length.19 The SUR1 mutations,D1193V and R1436Q (referred to as SUR1D1193V/R1436Q), and G228D and D1471 (referred to as SUR1G228D/D1471N),were made in the same SUR1 cDNA construct to mimic the fact that the patients had mutations on the same chromosome.Mouse Kir6·2 was used and expressed as described previously.41 Mouse Kir6·2-GFP (Kir6·2 fused in frame with the enhanced variant of the green fluorescent protein) and Kir6·2-HA (Kir6·2 engineered to contain an extracellular antigenic haemagglutinin epitope tag between the first transmembrane domain and the H5 segment) were kind gifts of Drs Ribalet and Jan, respectively. Login to comment
64 He was homozygous for two mutations in SUR1, namely D1193V and R1436Q, with both mutations occurring on each allele. Login to comment
93 In particular, SUR1D1193V/R1436Q was less efficiently transfected. Login to comment
95 In addition, in HEK293 cells we have not established a clear correlation between glycosylation pattern and trafficking status.48 We next examined the behaviour of SUR1D1193V, SUR1R1436Q and SUR1D1193V/R1436Q. Login to comment
103 We next examined the behaviour of SUR1D1193V, SUR1R1436Q and SUR1D1193V/R1436Q. Login to comment
114 SUR1D1193V and SUR1V1572I were functional in Rb86 flux assays whereas SUR1R1436Q, SUR1D1193V/R1436Q,SUR1G228D,SUR1D1471NandSUR1G228D/ D1471N were not (Fig. 4). Login to comment
120 SUR1D1193V, SUR1V1572I and SUR1D1471N were functional in patch clamp assays whereas SUR1R1436Q, SUR1D1193V/R1436Q, SUR1G228D and SUR1G228D/D1471N were not.In the knowledge of these results we repeated the flux assays and trafficking assays with Kir6·2-GFP with SUR1D1471N. Login to comment
128 Patient 1 had severe diffuse disease and was homozygous for two ABCC8 mutations in the cis configuration (SUR1D1193V/ R1436Q). Login to comment
141 The R1436Q mutation led to channel complexes present at the plasma membrane; however,under our assay conditions we were not able to demonstrate significant channel activity. Login to comment

PMID: 15807877 [PubMed] Ohkubo K et al: "Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy."

No. Sentence Comment

122 To date, only three kinds of SUR1 mutations (I446fsdelT, R1420C and R1436Q) have been reported in Japanese PHHI patients.20,42 We defined 11 novel mutations, and the SUR1 and Kir6.2 mutations account for about 80% of the PHHI cases in this study, although Tanizawa et al.20 reported only about 20% (three kinds of mutations in four patients from the screening of 17 PHHI patients) and Someya et al.42 did not detect any mutations (in eight PHHI patients). Login to comment

PMID: 10615958 [PubMed] Tanizawa Y et al: "Genetic analysis of Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy: nucleotide-binding fold-2 mutation impairs cooperative binding of adenine nucleotides to sulfonylurea receptor 1."

No. Sentence Comment

2 In the SUR1 gene, we identified one frameshift (I446fsdelT) and two missense (R1420C, R1436Q) mutations. Login to comment
4 Siblings homozygous for the R1420C mutation had a mild form, whereas two patients heterozygous for the I446fsdelT and R1436Q mutations, respectively, exhibited a severe form of PHHI. Login to comment
63 The R1436Q mutation created a BsrI restriction site (CCAGTG). Login to comment
64 After PCR amplification of exon9 (I446fsdelT)or exon 35 (R1420Cand R1436Q), the products were digested with the appropriate restriction enzymes and analyzed by electrophoresis on 2% agarose gel. Login to comment
67 Site-directed mutagenesis was performed using mutagenesis primers (for I446fsdelT: 5 -acg ctc cgt tca tgc ctc tcc atc atc c-3 ; for R1420C: 5 -gcc agt aca gat cat gtg ggc gtg atc ctc c-3 ; and for R1436Q: 5 -ttc agc ggc acc atc caa ttc aacctg gac cc-3 ) and a GeneEditor in vitro Site-DirectedMuta- genesisSystem (Promega, Madison, WI). Login to comment
81 We identified three potential disease-causing mutations (I446fsdelT, R1420C, and R1436Q). Login to comment
90 Two other mutations (R1420C and R1436Q) were missense mutations, both in NBF-2, a functionally important domain of SUR1. Login to comment
95 R1436Q is a novel missense mutation. Login to comment
120 Therefore, we introduced I446fsdelT, R1420C, and R1436Q mutations by site-directed mutagenesis to the corresponding positions of mouse SUR1 cDNA, and mutant SUR1 and mouse Kir6.2 were transiently coexpressed in COS-7 cells to reconstitute the mutant KATP channel. Login to comment
124 Because the R1436Q mutation is a missense mutation, the protein expression level of SUR1-1436Q was assessed by Western blot analysis. Login to comment
128 Activation ofthe channel by diazoxide also appeared to be impaired in the KATP(SUR1-1420C) mutant, TABLE 3 Profiles of patients with SUR1 gene mutations Onset Birth Treatment/ Patient Mutation (day) weight (g) outcome 1 I446fsdelT 0 5,014 Partial pancreatectomy 2 R1420C 0 5,254 Remission 3 R1420C 0 5,080 Remission 4 R1436Q 0 3,410 Partial pancreatectomy FIG. 1. Login to comment
160 This may also be the case for patient 4, who was heterozygous for a germline R1436Q mutation. Login to comment
66 Site-directed mutagenesis was performed using mutagenesis primers (for I446fsdelT: 5 -acg ctc cgt tca tgc ctc tcc atc atc c-3 ; for R1420C: 5 -gcc agt aca gat cat gtg ggc gtg atc ctc c-3 ; and for R1436Q: 5 -ttc agc ggc acc atc caa ttc aacctg gac cc-3 ) and a GeneEditor in vitro Site-DirectedMuta- genesisSystem (Promega, Madison, WI). Login to comment
80 We identified three potential disease-causing mutations (I446fsdelT, R1420C, and R1436Q). Login to comment
89 Two other mutations (R1420C and R1436Q) were missense mutations, both in NBF-2, a functionally important domain of SUR1. Login to comment
94 R1436Q is a novel missense mutation. Login to comment
119 Therefore, we introduced I446fsdelT, R1420C, and R1436Q mutations by site-directed mutagenesis to the corresponding positions of mouse SUR1 cDNA, and mutant SUR1 and mouse Kir6.2 were transiently coexpressed in COS-7 cells to reconstitute the mutant KATP channel. Login to comment
123 Because the R1436Q mutation is a missense mutation, the protein expression level of SUR1-1436Q was assessed by Western blot analysis. Login to comment
127 Activation ofthe channel by diazoxide also appeared to be impaired in the KATP(SUR1-1420C) mutant, TABLE 3 Profiles of patients with SUR1 gene mutations Onset Birth Treatment/ Patient Mutation (day) weight (g) outcome 1 I446fsdelT 0 5,014 Partial pancreatectomy 2 R1420C 0 5,254 Remission 3 R1420C 0 5,080 Remission 4 R1436Q 0 3,410 Partial pancreatectomy FIG. 1. Login to comment

PMID: 25555642 [PubMed] Bennett JT et al: "Molecular genetic testing of patients with monogenic diabetes and hyperinsulinism."

No. Sentence Comment

121 "Hypoglycemia"* - 1 PATH - - [15] c.4135CNA p.R1379S NDM rs137852673 1 PATH - PATH ClinVar c.4307GNA p.R1436Q n.p. rs387906407 2 PATH PATH PATH [43] c.4543ANG p.T1515A CHI - 1 LP - - This report KCNJ11 c.137ANG p.H46R NDM - 1 PATH - - [44] c.143ANT p.N48I NDM - 2 PATH - - [25] c.497GNA p.C166Y NDM rs80356618 1 PATH - PATH [45] c.601CNT p.R201C NDM rs80356625 1 PATH - PATH [17] c.602GNA p.R201H NDM rs80356624 1 PATH VUS - [45] c.616CNT p.R206C CHI - 1 LP - - This report c.637GNA p.A213T CHI - 1 PATH - - [46] c.685GNA p.E229K NDM - 1 PATH - - [30] c.691GNC/c.970GNA p.V231L/p.G324R NDM -/- 1/1 VUS/VUS -/- -/- This report/this report INS c.-331delC p.? Login to comment

PMID: 25584046 [PubMed] Arya VB et al: "Congenital hyperinsulinism: clinical and molecular characterisation of compound heterozygous ABCC8 mutation responsive to Diazoxide therapy."

No. Sentence Comment

83 Muzyamba et al. showed that single SUR1 mutants (D1193V or R1436Q) trafficked to the plasma membrane whereas the double mutant (SUR1D1193V/ R1436Q) was retained in the endoplasmic reticulum [16]. Login to comment