ABCMdb

PMID: 25201519

Arya VB, Guemes M, Nessa A, Alam S, Shah P, Gilbert C, Senniappan S, Flanagan SE, Ellard S, Hussain K
Clinical and histological heterogeneity of congenital hyperinsulinism due to paternally inherited heterozygous ABCC8/KCNJ11 mutations.
Eur J Endocrinol. 2014 Dec;171(6):685-95. doi: 10.1530/EJE-14-0353. Epub 2014 Sep 8., [PubMed]

Sentences

No. Mutations Sentence Comment

63 ABCC8 p.Glu128Lys ABCC8 p.Arg74Trp ABCC8 p.Gln54* ABCC8 p.Met429* ABCC8 p.Ser12* Extracellular M1V S12X Q54X E128K R74W M429X H627fs D855E R934X K890fs E995X *A1185V D1194V *L1431F R1437Q *D1472N A1493T *A1508P *E1507K *R54H R136fs Kir6.2 SUR1 CL3 linker Walker A p.? Login to comment 70 ABCC8 p.Gly111Arg ABCC8 p.Ala113Val ABCC8 p.Ala1263Thr (c.1629-2A>C) Walker B *R177W *M209I *I284del E292K T294M G312C COOH COOH NH2 M1 M2 6 1 TMD0 TMD1 TMD2 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 p.*391Rext*94 *T62M R1494W Q954X G111R A113V *V601I *A1153T D1031N L1171X A1263T V185fs Intracellular NH2 NBD2 NBD1 Cell membrane Figure 1 Paternal mutations mapped onto the SUR1 and Kir6.2 protein. Login to comment 74 ABCC8 p.Gly111Arg ABCC8 p.Glu128Lys ABCC8 p.Gln54* ABCC8 p.Ala113Val ABCC8 p.Ser12* ABCC8 p.Val601Ile Patient ID GA (weeks), birth weight (g) Gender Age at presentation (weeks) Blood glucose (mmol/l) Serum insulin (mU/l) Mutation protein description (DNA description) LOH Dzx Resp PET CT/PVS Outcome ABCC8 1 40, 3150 Male 52 2.4 4.3 L1431F/N (c.4291COT/N) Yes - On Dzx at 6.4 years 2 40, 4000 Male 2 2.4 1.9 p.?/N (c.2697C4AOT/N) Yes - Off Dzx at 2 years 3 40, 5010 Female !1 2.6 8.6 E1507K/N (c.4519GOA/N) Yes - On Dzx at 2.3 years 4 40, 5600 Male !1 2.0 7.5 A1508P/N (c.4522GOC/N) Yes - On Dzx at 12 years 5 37, 4820 Male !1 2.0 9.0 A1153T/N (c.3457GOA/N) Yes - On Dzx at 4 years 6 38, 3630 Female 72 3.1 !2 A1153T/N (c.3457GOA/N) Yes - On Dzx at 2 years 8 35, 2820 Male !1 1.2 12.9 A1185V/N (c.3554COT/N) Yes - Off Dzx at 8 months 9 36, 4450 Male !1 2 28.5 p.?/N (c.3992-9GOA/N) Yes - Off Dzx after 4.5 months 10 41, 2780 Female !1 1 9.3 D1472N/N (c.4414GOA/N) Yes - Off Dzx after 10 months 11 38, 3750 Male !1 2.6 5.90 V601I/N (c.1801GOA/N) Yes - Off Dzx after 14 months 13 40, 4160 Female !1 2.4 14.8 V185fs/N (c.554delT/N) No Diffuse Off octreotide at 5 years 14 37, 3090 Male !1 0.6 12.4 p.?/N (c.3992-9GOA/N) No Focal On octreotide at 9.5 years 15 40, 3600 Male !1 2.7 6.7 H627fs/N (c.1879delC/N) No Diffuse Off octreotide at 18 months 16 40, 4700 Female !1 2.0 !2 E1507K/N (c.4519GOA/N) NA - No treatment required 17 40, 4200 Male !1 1.0 !2 D1031N/N (c.3091GOA/N) NA - No treatment required 18 41, 4850 Male !1 1.2 10.1 M1V/N (c.1AOG/N) No Diffuse (PVS) Near-total pancreatectomy (95%) 19 38, 2400 Male !1 2.1 16.3 D1194V; R1437Q/N (c.3581AOT; c.4310GOA/N) Yes No Focal Hypoglycaemia resolved after removal of focal lesion 20 40, 4580 Female !1 1.1 103 A1493T/N (c.4477GOA/N) Yes a No Diffuse Near-total pancreatectomy (95%) 21 40, 4600 Male !1 1.2 22.5 K890fs/N (c.2669_2675del/N) Yes No Focal Hypoglycaemia resolved after removal of focal lesion 22 40, 4335 Male !1 2.6 3.4 p.?/N (c.3992-9GOA/N) Yes No Focal Partial pancreatectomy 23 40, 3030 Male !1 1.8 15.6 p.?/N (c.3992-9GOA/N) Yes No Focal Partial pancreatectomy 24 40, 2770 Male !1 2.2 3.4 p.?/N (c.580-1GOC/N) No Indeterminate (PVS) Partial pancreatectomy - focal lesion on histology 25 41, 4290 Male 2 2.3 4.32 E128K/N (c.382GOA/N) No Focal Hypoglycaemia resolved after removal of focal lesion 27 40, 5095 Male !1 2.0 10.5 L1171X/N (c.3512delT/N) Yes No Focal Hypoglycaemia resolved after removal of focal lesion 29 37, 3560 Male !1 1.6 21.8 p.?/N (c.1629-2AOC/N) No Focal Hypoglycaemia resolved after removal of focal lesion 30 40, 2750 Male !1 1.5 16.4 G111R/N (c.331GOA/N) Yes No Focal Hypoglycaemia resolved after removal of focal lesion 31 37, 3340 Male !1 2.1 15 H627fs/N (c.1879delC/N) Yes No Focal Hypoglycaemia resolved after removal of focal lesion 32 41, 4950 Male !1 1.2 11.95 R934X/N (c.2800COT/N) No Focal Hypoglycaemia resolved after removal of focal lesion 33 40, 3080 Female 12 1.5 4.6 S12X/N (c.35COA/N) Yes No Focal Hypoglycaemia resolved after removal of focal lesion 34 39, 3600 Male !1 2.5 8 R1494W/N (c.4480COT/N) No Diffuse (PVS) Near-total pancreatectomy (95%) 37 36, 3410 Male !1 0.9 17.42 R1494W/N (c.4480COT/N) No Focal Partial pancreatectomy Table 1 Continued Patient ID GA (weeks), birth weight (g) Gender Age at presentation (weeks) Blood glucose (mmol/l) Serum insulin (mU/l) Mutation protein description (DNA description) LOH Dzx Resp PET CT/PVS Outcome 38 39, 4900 Female !1 1.4 23.61 A113V/N (c.338COT/N) No Diffuse (PVS) Near-total pancreatectomy (95%) 39 36, 3210 Male !1 0.6 114 Mosaic Q54X (c.160COT) No Diffuse Near-total pancreatectomy (95%) 40 41, 4300 Female !1 2.1 17 Q954X/N (c.2860COT/N) No Diffuse Near-total pancreatectomy (95%) 41 36, 2730 Male !1 ? Login to comment 76 ABCC8 p.Arg74Trp ABCC8 p.Ala1263Thr ABCC8 p.Met429* ABCC8 p.Met429* p.?/N (c.1333-1013AOG/N) Yes No Focal Hypoglycaemia resolved after removal of focal lesion 42 37, 4480 Female !1 1.7 5.6 A1263T/N (c.3787GOA/N) No Diffuse (PVS) Near-total pancreatectomy (95%) 45 39, 3960 Male !1 2.4 23.6 p.?/N (c.1-?_c.1176C1?/N) No Focal Hypoglycaemia resolved after removal of focal lesion 46 34, 3800 Male !1 0.8 201 D855E/N (c.2565COA/N) No Focal Hypoglycaemia resolved after removal of focal lesion 47 41, 4780 Male !1 2.4 15.9 M429X/N (c.1254_1284dup/N) No Focal Hypoglycaemia resolved after removal of focal lesion 48 40, 3800 Female !1 2.4 5.9 M429X/N (c.1254_1284dup/N) No Diffuse On octreotide at 7 months 49 40, 4100 Male !1 0.8 9.1 R74W/N (c.220COT/N) No Focal Hypoglycaemia resolved after removal of focal lesion 51 38, 3730 Female !1 1.9 21.6 E995X (c.2983GOT) No Focal Hypoglycaemia resolved after removal of focal lesion KCNJ11 7 38, 3780 Female !1 1.7 29.6 M209I/N (c.627GOA/N) Yes Diffuse On Dzx at 2.8 years 12 40, 3450 Male !1 2 6.7 R54H/N (c.161GOA/N) Yes - Off Dzx after 4 months 26 36, 3880 Male !1 !1.0 6.1 E292K/N (c.874GOA/N) No Diffuse (PVS) Near-total pancreatectomy (95%) 28 40, 4600 Male !1 1.3 38.87 R136fs/N (c.405dupG/N) No Diffuse (PVS) Near-total pancreatectomy (95%) 35 38, 4120 Female !1 2.2 12.0 T294M/N (c.881COT/N) No Diffuse (PVS) Near-total pancreatectomy (95%) 36 37, 3960 Male !1 1.9 7.0 G312C/N (c.934GOT/N) No Focal Hypoglycaemia resolved after removal of focal lesion 43 40, 4100 Female !1 1.0 35 I284del/N (c.850_852delATC/N) Yes Diffuse Off Dzx at 4 years of age 44 40, 4580 Female 32 2.2 7 p.*391Rext*94/N (c.1171TO C/N) No Focal Partial pancreatectomy, currently on Dzx 50 37, 3980 Male !1 0.5 2.9 T62M/N (c.185COT/N) Yes - Off Dzx at 1 month 52 40, 5190 Male !1 2.5 8.4 R177W/N (c.529AOT/N) Yes Diffuse On Dzx at 3 months of age 53 40, 3920 Male !1 2.1 9.2 E292K/N (c.874GOA/N) Yes Diffuse Off Dzx at 5 months of age Dzx, diazoxide; PET, positron emission tomography; PVS, pancreatic venous sampling; GA, gestational age; Wt, weight; LOH, loss of heterozygosity; Resp, responsiveness. Login to comment 114 ABCC8 p.Val601Ile (c.3992-9GOA) No Not available Not available Disease causing (5)a D1472N (c.4414GOA) Yes Deleterious Damaging Disease causing (24)a V601I (c.1801GOA) No Neutral Tolerated Disease causing Novela V185fs (c.554delT) Yes Not available Not available Disease causing Novel H627fs (c.1879delC) No Not available Not available Disease causing (9)a D1031N (c.3091GOA) No Neutral Tolerated Disease causing Novel M1V (c.1AOG) No Neutral Damaging Disease causing (6)a A1493T (c.4477GOA) Yes Deleterious Damaging Disease causing (14)a R1494W (c.4480COT) Yes Deleterious Damaging Disease causing (25)a KCNJ11 M209I (c.627GOA) No Neutral Damaging Disease causing Novel R54H (c.161GOA) No Deleterious Damaging Disease causing Novela E292K (c.874GOA) No Deleterious Damaging Disease causing Novel T62M (c.185COT) No Deleterious Damaging Disease causing (4) R177W (c.529AOT) No Deleterious Damaging Disease causing Novel a These patients were included in reference (3). 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