ABCMdb

ABCC8 p.Met1394Arg

Predicted by SNAP2:	A: D (66%), C: D (59%), D: D (91%), E: D (85%), F: D (66%), G: D (80%), H: D (80%), I: N (93%), K: D (85%), L: N (82%), N: D (85%), P: D (91%), Q: D (75%), R: D (85%), S: D (75%), T: D (75%), V: N (72%), W: D (80%), Y: D (66%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D,

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Publications
[hide] Co-inheritance of two ABCC8 mutations causing an u... Gene. 2013 Mar 1;516(1):122-5. doi: 10.1016/j.gene.2012.12.055. Epub 2012 Dec 22. Faletra F, Snider K, Shyng SL, Bruno I, Athanasakis E, Gasparini P, Dionisi-Vici C, Ventura A, Zhou Q, Stanley CA, Burlina A
Co-inheritance of two ABCC8 mutations causing an unresponsive congenital hyperinsulinism: clinical and functional characterization of two novel ABCC8 mutations.
Gene. 2013 Mar 1;516(1):122-5. doi: 10.1016/j.gene.2012.12.055. Epub 2012 Dec 22., [PMID:23266803]

Abstract [show]
Congenital hyperinsulinism (CHI) occurs as a consequence of unregulated insulin secretion from the pancreatic beta-cells. Severe recessive mutations and milder dominant mutations have been described in the ABCC8 and KCNJ11 genes encoding SUR1 and Kir6.2 subunits of the beta-cell ATP-sensitive K(+) channel. Here we report two patients with CHI unresponsive to medical therapy with diazoxide. Sequencing analysis identified a compound heterozygous mutation in ABCC8 in both patients. The first one is a carrier for the known mild dominant mutation p.Glu1506Lys jointly with the novel mutation p.Glu1323Lys. The second carries the p.Glu1323Lys mutation and a second novel mutation, p.Met1394Arg. Functional studies of both novel alleles showed reduced or null cell surface expression, typical of recessive mutations. Compound heterozygous mutations in congenital hyperinsulinism result in complex interactions. Studying these mechanisms can improve the knowledge of this disease and modify its therapy.

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Sentences [show]
No. Sentence Comment
5 The second carries the p.Glu1323Lys mutation and a second novel mutation, p.Met1394Arg. Login to comment
81 In addition he has a novel variant, p.Met1394Arg (c.4181T>G). Login to comment
88 As Fig. 2A shows neither the E1323K nor the M1394R mutants are glycosylated appropriately in comparison to the WT, indicating that these mutants probably cause trafficking defects and are likely retained in the endoplasmic reticulum. Login to comment
94 COSm6 cells were co-transfected with cDNAs for Kir6.2 and WT-flagSUR1, the M1394R-flagSUR1 or the E1323K-flagSUR1. Login to comment
105 F. Faletra et al. / Gene 516 (2013) 122-125 is expressed at the surface at a low level (16.98&#b1;4.87%) but the presence of the M1394R mutant is nearly obliterated at the cell surface (Fig. 2B). Login to comment
107 3A and B and note the current amplitude scale difference), but no currents were observed in cells expressing the M1394R mutant after more than 10 patches. Login to comment
116 In patient 2, who is compound heterozygous for the p.[Glu1323Lys]: [Met1394Arg] mutations, both defects seem to have a recessive inheritance and impair the channel trafficking to the plasma membrane, even though E1323K does have normal gating properties. Login to comment