ABCMdb

ABCC8 p.Val1523Leu

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Publications

PMID: 17919176 [PubMed] Patch AM et al: "Mutations in the ABCC8 gene encoding the SUR1 subunit of the KATP channel cause transient neonatal diabetes, permanent neonatal diabetes or permanent diabetes diagnosed outside the neonatal period."

No. Sentence Comment

149 [14] 120T229Iþ V1523L [c.686C>T]þ [c.4567G>T] Compound heterozygous PNDMCanada4N/AYesEllardetal. Login to comment
161 Affected probands and family members can be separated into three distinct groups based T229I/T229I ABCC8 mutations Transient Neonatal Diabetes Mellitus Recessive homozygous mutations R826W (2) H1024Y R1183Q (2) R1183W (5) R1314H R1380C (3) R1380H R1380L (2) D209E D212I D212N R306H V324M C435R L451P L582V (2) Dominant heterozygous mutations Permanent Neonatal Diabetes Mellitus E382K/E382K A1185E/A1185E Mosaic N72S Recessive homozygous or mosaic mutations P45L/G1401R E208K/Y263D T229I/V1523L L438F/M1290V P207S/c.536del4 E1327K+V1523A/ c.1327ins10 Recessive compound heterozygous mutations 1K Dominant heterozygous mutations D209E Q21 L213R L225P(2) I1425V V86A V86G F132L (2) F132V L135P Fig. 2 A diagram illustrating the inheritance of ABCC8 mutations in probands with permanent and transient forms of neonatal diabetes. Login to comment
163 Permanent Neonatal Diabetes Mellitus Transient Neonatal Diabetes Mellitus 1 5 10 15 20 25 30 35 39 N72S V86A V86G F132L F132V L135PP45L P207S E208K D209E Q211K L213R L225P T229I Y263D D209E D212I D212N T229I R306H V324M L438F L451P E382K R826W R1183W R1183Q A1185E E1327K R1314H M1290V R1380C R1380H R1380L G1401R V1523A V1523L H1024YC435R L582V I1425V Fig. 3 The location of missense mutations causing neonatal diabetes within the coding sequence of ABCC8. Login to comment
243 This mutation has previously been found in a child with PNDM who is a compound heterozygote for T229I and V1523L. Login to comment
244 Functional studies of heterozygous mutant channels suggested that V1523L has a greater effect on ATP sensitivity than T229I [14] and is consistent with the more severe PNDM phenotype caused by the T229I/V1523L genotype. Login to comment
247 Functional data have only been published for 8/39 ABCC8 missense mutations to date (F132L [16]; I1425V and H1024Y [13]; mutations (P207S, T229I, A1185E and V1523L [14]; L225P [16]). Login to comment

PMID: 21989597 [PubMed] Bowman P et al: "Heterozygous ABCC8 mutations are a cause of MODY."

No. Sentence Comment

60 V1523L (proband 5) was previously identified in a patient with PNDM who was a compound heterozygote for V1523L and T229I [5]. Login to comment
62 Two of the novel mutations, N1245D and E100K (probands 4 and 7), were inherited from a diabetic parent but grandparental samples were not available to check cosegregation. Login to comment
65 Since the V222M mutation has previously been seen in a patient with hyperinsulinism (S. Ellard and S. Flanagan, unpublished data), G214R cannot be an inactivating mutation as this would result in a hyperinsulinism phenotype and not diabetes. Login to comment
73 N/M 19 SU 50s Family 1 R1380H/N Family 2 R1380H/N 50s OHA 21 Ins 40s OHA N/M 33 SU N/M 11 SU N/M 18 SU SB Family 3 V222M/G214R V222M/N 45 V222M/G214R 15 Ins Family 4 N1245D/N Family 6 Q485R/N Family 5 V1523L/N Family 7 E100K/N N/M 36 SU N/M 14 Ins N/M 40s OHA 60s Diet N/M 13 SU N/N N/N N/M 42 OHA & Ins N/N 60s Diet N/M 60s Diet ×2 SU Fig. 1 Partial pedigrees showing affected family members, genetic status and treatment (where known). Login to comment
78 N/M 19 SU 50s Family 1 R1380H/N Family 2 R1380H/N 50s OHA 21 Ins 40s OHA N/M 33 SU N/M 11 SU N/M 18 SU SB Family 3 V222M/G214R V222M/N 45 V222M/G214R 15 Ins Family 4 N1245D/N Family 6 Q485R/N Family 5 V1523L/N Family 7 E100K/N N/M 36 SU N/M 14 Ins N/M 40s OHA 60s Diet N/M 13 SU N/N N/N N/M 42 OHA & Ins N/N 60s Diet N/M 60s Diet &#d7;2 SU Fig. 1 Partial pedigrees showing affected family members, genetic status and treatment (where known). Login to comment

PMID: 17668386 [PubMed] Ellard S et al: "Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects."

No. Sentence Comment

39 Three probands were compound heterozygotes for the missense mutations P45L/G1401R (ISPAD 47), E208K/Y263D (ISPAD 119), and T229I/V1523L (ISPAD 120). Login to comment
64 Compared with homomeric A1185E or T229I/V1523L channels, the heterozygous A1185E, T229I, and V1523L channels showed greater ATP sensitivity and smaller KATP currents at 3 mM MgATP (see fig. 6). Login to comment
73 Details of ABCC8 Mutations and Clinical Information ISPAD Number Mutation (Protein Effect) Nucleotide Change Zygosity Age at Diagnosis (wk) Birth Weighta (Percentile) Neurological Feature Developmental Delay Muscle Weakness Epilepsy 123 V86Ab c.257TrC Heterozygous 8 2,900 (9) No No No 124 V86G c.257TrG Heterozygous 5 2,900 (13) No No No 68 F132Lb c.394TrC Heterozygous 13 2,200 (!1) Yes Yes Yes 125 F132L c.394TrC Heterozygous 26 2,440 (9) Yes Yes No 82 F132V c.394TrG Heterozygous 20 NA No No No 46 D209E c.627CrA Heterozygous 5 2,720 (13) No No No 134 Q211Kb c.631CrA Heterozygous 16 2,400 (3) No No No 122 L225Pc c.674TrC Heterozygous 4 2,500 (11) No No No 117 E382K c.1144GrA Homozygous 8 2,700 (4) No No No 118 A1185E c.3554CrA Homozygous 0 4,200 (95) No Yes Yes 116 N72S c.215ArG Mosaic 5 3,870 (74) No No No 47 P45L ϩ G1401R [c.134CrT] ϩ [c.4201GrA] Compound heterozygous 6 2,520 (18) Yes Yes No 119 E208K ϩ Y263D [c.622GrA] ϩ [c.787TrG] Compound heterozygous 13 2,950 (28) Yes No No 120 T229I ϩ V1523L [c.686CrT] ϩ [c.4567GrT] Compound heterozygous 4 NA No No No 78 P207S ϩ Y179X [c.619CrT] ϩ [c.536_539delATGG] Compound heterozygous 8 3,290 (29) No No No 121 [E1327K; V1523A] ϩ T1043QfsX74 [c.3979GrA; 4568CrT] ϩ [c.3127_3129delACCinsCAGCCAGGACCTG] Compound heterozygous 1 2,380 (!1) No No No a NA p not available. Login to comment
94 To simulate the patient`s genotype, we coinjected Kir6.2 mRNA with hetF132L (1:1 mix of WT and F132L SUR1 mRNAs); homA1185E or P207S (mutant SUR1 only); or V1523LϩT229I (1:1 mix of V1523L and T229I SUR1). Login to comment
134 To simulate the compound heterozygous state of hetSUR1-T229IϩhetSUR1-V1523L, Kir6.2 was coexpressed with a 1:1 mixture of SUR1-T229I and SUR1-V1523L mRNAs. Login to comment
95 To simulate the patient`s genotype, we coinjected Kir6.2 mRNA with hetF132L (1:1 mix of WT and F132L SUR1 mRNAs); homA1185E or P207S (mutant SUR1 only); or V1523Laf9;T229I (1:1 mix of V1523L and T229I SUR1). Login to comment
137 To simulate the compound heterozygous state of hetSUR1-T229Iaf9;hetSUR1-V1523L, Kir6.2 was coexpressed with a 1:1 mixture of SUR1-T229I and SUR1-V1523L mRNAs. Login to comment