ABCMdb

ABCC8 p.Ala478Asp

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Publications

PMID: 21536946 [PubMed] Macmullen CM et al: "Diazoxide-unresponsive congenital hyperinsulinism in children with dominant mutations of the beta-cell sulfonylurea receptor SUR1."

No. Sentence Comment

97 Direct sequencing of genomic DNA from the proband, his affected mother, and younger brother revealed a single heterozygous A478D mutation in exon 9 of ABCC8 (SUR1) (Fig. 1). Login to comment
148 Parent of origin Family 1 II-1 LGA 1 No Diffuse Q474R De novo Family 2 II-1 LGA 1 No Diffuse A478D Maternal Family 2 II-2 AGA 1 No Diffuse A478D Maternal Family 3 II-1 AGA 1 No Diffuse V715A Maternal Family 3 II-2 LGA 1 No No surgery V715A Maternal Family 4 II-1 LGA 1 No No surgery V715G Not maternal Family 5 II-1 LGA 1 No Diffuse V715G De novo Family 6 II-1 LGA 42 No Diffuse V715G De novo Family 7 II-1 LGA 5 No Diffuse G716D Not maternal Family 8 II-1 AGA 3 No Diffuse T888P De novo Family 9 II-1 AGA 2 No Diffuse G1384E De novo Family 10 II-1 LGA 1 No Diffuse S1387F De novo Family 11 II-1 LGA 1 No Diffuse S1387Y De novo Family 12 II-1 LGA 1 No Diffuse S1389Y De novo Family 13 II-1 SGA 180 No Diffuse A1458T Paternal Family 14 II-1 LGA 88 No Diffuse Q1459H De novo Family 15 II-1 AGA 167 No Diffuse E1517K Maternal Dominant diazoxide-unresponsive (n = 17) 65% LGA median 1 day range (1-180 days) 100% no Diffuse 5 of 17 maternal 1 of 17 paternal 9 of 17 de novo 2 of 17 not maternal Dominant diazoxide-responsive (n = 13) 77% LGA median 30 days range (1-1,215 days) 100% yes Diffuse 5 of 13 maternal 4 of 13 paternal 4 of 13 de novo Recessive (n = 48) 87% LGA median 1 day range (1-9 days) 100% no Diffuse 48 of 48 biallelic LGA, AGA, SGA 5 large, appropriate, small for gestational age. Login to comment
189 The important distinction between dominant and recessive missense mutations of the ABCC8 gene that cause hyperinsulinism appears to be whether they produce SUR1 subunits that can combine with Kir6.2 and then be trafficked to the TABLE 2 Mutant protein biogenesis and activity Surface expression (% of wild-type channel level) MgADP stimulation (% current in 0.1 mmol/L ATP plus 0.5 mmol/L ADP) Diazoxide stimulation (% current in 0.1 mmol/L ATP plus 0.2 mmol/L diazoxide) Mutation 1) Q474R 119.12 6 13.87 3.16 6 1.34 (n = 3) 2.03 6 0.77 (n = 3) 2) A478D 83.67 6 5.33 0.69 6 0.27 (n = 6) 3.14 6 1.37 (n = 3) 3) V715A 83.00 6 5.29 0.53 6 0.28 (n = 3) 1.73 6 0.53 (n = 4) 4) V715G 96.33 6 3.18 0.28 6 0.16 (n = 3) 2.35 6 1.99 (n = 3) 5) G716D 66.67 6 5.24 2.39 6 1.90 (n = 6) 2.37 6 1.32 (n = 4) 6) T888P 54.33 6 5.33 0.38 6 0.30 (n = 3) 1.30 6 0.44 (n = 3) 7) G1384E 101.80 6 8.50 0.17 6 0.09 (n = 4) 1.64 6 0.49 (n = 4) 8) S1387F 83.91 6 5.30 0.84 6 0.17 (n = 4) 4.05 6 1.34 (n = 4) 9) S1387Y 83.13 6 5.38 2.46 6 0.96 (n = 4) 2.44 6 0.42 (n = 4) 10) S1389Y 70.00 6 7.81 1.26 6 0.73 (n = 4) 1.65 + 0.63 (n = 3) 11) A1458T 94.33 6 10.48 0.52 6 0.21 (n = 3) 1.06 6 0.37 (n = 3) 12) Q1459H 91.00 6 2.31 0.69 6 0.39 (n = 3) 1.32 6 0.29 (n = 3) 13) E1517K 72.88 6 5.85 1.73 6 0.39 (n = 3) 1.96 6 0.55 (n = 4) Mean of dominant diazoxide-unresponsive SUR1 mutations 84.6 6 4.64 (n = 13) 1.42 6 0.35 (n = 13)* 1.83 6 0.18 (n = 13)† Mean of dominant diazoxide-responsive SUR1 mutations 93.68 6 5.07 (n = 10) 14.52 6 5.15 (n = 10) 18.33 6 6.06 (n = 10) Wild type 100 61.19 6 5.53 (n = 11) 77.8 6 2.2 (n = 9) Data are means 6 SE. Login to comment

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

No. Sentence Comment

120 Gene Nucleotide Protein Pheno dbSNP Times seen Interp. LOVD ClinVar Reference ABCC8 c.1277ANG/c.3545GNA p.N426S/p.R1182Q NDM -/rs193922400 1/2 VUS/PATH -/- -/LP This report/[9] c.1433CNA p.A478D CHI - 1 PATH - - [41] c.1608TNG p.F536L NDM - 1 LP - - This report c.2422CNA p.Q808K "DM1"* rs202189540 1 LB - - This report c.2506CNT/c.4138_4140delinsCA p.R836*/p.T1380Qfs*80 CHI rs72559722/- 1/1 PATH/PATH -/- -/- [42]/this report c.3976GNA p.E1326K CHI rs200563930 1 VUS - - [8] ex 32 del p.? Login to comment