ABCMdb

PMID: 21214702

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., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCC8 p.Val84Ile 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 ABCC8 p.Val84Ile 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 ABCC8 p.Val84Ile 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 ABCC8 p.Val84Ile The V84I mutation was not found in 300 control chromosomes of Czech healthy subjects. Login to comment 61 ABCC8 p.Val84Ile Seven of nine additional family members tested were found to carry the V84I mutation (Fig. 1; Table 1). Login to comment 62 ABCC8 p.Val84Ile 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 ABCC8 p.Val84Ile 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 ABCC8 p.Val84Ile 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 ABCC8 p.Val84Ile 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 ABCC8 p.Val84Ile 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