ABCMdb

ABCC8 p.Val84Ile

Predicted by SNAP2:	A: N (66%), C: N (78%), D: N (57%), E: N (53%), F: N (57%), G: N (57%), H: N (53%), I: N (97%), K: D (59%), L: N (93%), M: N (87%), N: N (53%), P: D (59%), Q: N (57%), R: N (66%), S: N (61%), T: N (72%), W: D (63%), Y: N (87%),
Predicted by PROVEAN:	A: N, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: N, W: D, Y: D,

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Publications
[hide] Familial mild hyperglycemia associated with a nove... Pediatr Diabetes. 2011 May;12(3 Pt 2):266-9. doi: 10.1111/j.1399-5448.2010.00719.x. Epub 2011 Jan 9. Gonsorcikova L, Vaxillaire M, Pruhova S, Dechaume A, Dusatkova P, Cinek O, Pedersen O, Froguel P, Hansen T, Lebl J
Familial mild hyperglycemia associated with a novel ABCC8-V84I mutation within three generations.
Pediatr Diabetes. 2011 May;12(3 Pt 2):266-9. doi: 10.1111/j.1399-5448.2010.00719.x. Epub 2011 Jan 9., [PMID:21214702]

Abstract [show]
We present a unique case of a 19-year-old man with a positive family history of persistent mild hyperglycemia and a novel V84I mutation in ABCC8. The proband was initially detected to have fasting hyperglycemia (ranging 6.1-6.4 mmol/L) at the age of 12 years. Increased fasting blood glucose was also subsequently detected in five additional family members (in his twin brother, sister, mother, maternal aunt, and grandfather). The grandfather has been known to have mild diabetes since 30 years and has never been treated. After having excluded a causative mutation in five maturity-onset diabetes of the young genes (MODY1-4 and 6), we identified a novel ABCC8 V84I mutation, which segregated with autosomal dominant transmission of mild hyperglycemia within three generations. This mutation that is located in a conserved area of transmembrane domain TMD0 seems to be a rare cause of clinical phenotype resembling glucokinase-deficient diabetes.

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Sentences [show]
No. Sentence Comment
3 We present a unique case of a 19-year-old man with a positive family history of persistent mild hyperglycemia and a novel V84I mutation in ABCC8. Login to comment
7 After having excluded a causative mutation in five maturity-onset diabetes of the young genes (MODY1-4 and 6), we identified a novel ABCC8 V84I mutation, which segregated with autosomal dominant transmission of mild hyperglycemia within three generations. Login to comment
58 After having excluded a mutation within the GCK and HNFs genes or a change in gene dosage, we identified a novel G>A substitution in exon 2 of the ABCC8 gene leading to a substitution of valine (GTC) by isoleucine (ATC) at the first position of codon 84 (p.V84I mutation). Login to comment
60 The V84I mutation was not found in 300 control chromosomes of Czech healthy subjects. Login to comment
61 Seven of nine additional family members tested were found to carry the V84I mutation (Fig. 1; Table 1). Login to comment
62 Discussion We present a family with transmission of mild nonprogressive hyperglycemia in three generations because of a novel ABCC8 V84I mutation. Login to comment
63 The proband and five members of his family with mild hyperglycemia but no diabetic complications were found to carry the novel V84I mutation, which is located in ABCC8 exon 2 and leads to an aminoacid substitution in the transmembrane domain TMD0 of SUR1. Login to comment
67 We can therefore hypothesize that the V84I mutation may lead to slightly altered channel gating and thus impaired release of insulin granules. Login to comment
68 However, the V84I mutation that we report seems to induce a milder phenotype compared to other mutations in the TMD0 region described so far. Login to comment
69 The clinical phenotype of family members carrying the ABCC8 V84I mutation resembles GCK diabetes (MODY2) with an autosomal dominant mode of inheritance and persistent mild fasting hyperglycemia. Login to comment