ABCMdb

ABCC8 p.Ser574Gly

Predicted by SNAP2:	A: N (82%), C: D (63%), D: N (87%), E: N (93%), F: D (75%), G: N (82%), H: N (61%), I: D (53%), K: N (82%), L: D (53%), M: N (53%), N: N (87%), P: N (53%), Q: N (87%), R: N (72%), T: N (87%), V: N (57%), W: D (85%), Y: D (75%),
Predicted by PROVEAN:	A: N, C: D, D: N, E: N, F: D, G: N, H: N, I: D, K: N, L: D, M: D, N: N, P: N, Q: N, R: N, T: N, V: D, W: D, Y: D,

[switch to compact view]
Comments [show]

None has been submitted yet.

Publications
[hide] Therapeutic implications of novel mutations of the... Pharmacogenomics J. 2015 Feb;15(1):49-54. doi: 10.1038/tpj.2014.37. Epub 2014 Jul 22. Artuso R, Provenzano A, Mazzinghi B, Giunti L, Palazzo V, Andreucci E, Blasetti A, Chiuri RM, Gianiorio FE, Mandich P, Monami M, Mannucci E, Giglio S
Therapeutic implications of novel mutations of the RFX6 gene associated with early-onset diabetes.
Pharmacogenomics J. 2015 Feb;15(1):49-54. doi: 10.1038/tpj.2014.37. Epub 2014 Jul 22., [PMID:25048417]

Abstract [show]
Identification of the genetic defect underlying early-onset diabetes is important for determining the specific diabetes subtype, which would then permit appropriate treatment and accurate assessment of recurrence risk in offspring. Given the extensive genetic and clinical heterogeneity of the disease, high-throughput sequencing might provide additional diagnostic potential when Sanger sequencing is ineffective. Our aim was to develop a targeted next-generation assay able to detect mutations in several genes involved in glucose metabolism. All 13 known MODY genes, genes identified from a genome-wide linkage study or genome-wide association studies as increasing the risk of type 2 diabetes and genes causing diabetes in animal models, were included in the custom panel. We selected a total of 102 genes by performing a targeting re-sequencing in 30 patients negative for mutations in the GCK, HNF1alpha, HNF4alpha, HNF1beta and IPF1 genes at the Sanger sequencing analysis. Previously unidentified variants in the RFX6 gene were found in three patients and in two of them we also detected rare variants in WFS1 and ABCC8 genes. All patients showed a good therapeutic response to dipeptidyl peptidase-4 (DPP4) inhibitors. Our study reveals that next-generation sequencing provides a highly sensitive method for identification of variants in new causative genes of diabetes. This approach may help in understanding the molecular etiology of diabetes and in providing more personalized treatment for each genetic subtype.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
105 Variants identified in patients Patient Total variants Rs (SNPs) Rs OMIM associated Parents Rare variants Mother Father Case #1 578 136 rs5219 (KCNJ11 c.67G4A p.Glu23Lys) rs1169288 (HNF1A c.79A4C p.Ile27Leu) rs1169305 (HNF1A c.1720A4G p.Ser574Gly) rs1260326 (GCKR c.1403C4T p.Pro446Leu) rs5219 rs1169288 rs1169305 rs1260326 rs5219 rs1169288 rs1169305 rs1260326 RFX6 (c.1678G4A p.Asp560Asn) WFS1 (c.2054G4A p.Arg685His) both inherited from the mother Case #2 1032 182 rs5219 (KCNJ11 c.67G4A p.Glu23Lys) rs1169288 (HNF1A c.79A4C p.Ile27Leu) rs1169305 (HNF1A c.1720A4G p.Ser574Gly) NA NA RFX6 (c.1865C4A p.Thr622Lys) Case #3 614 135 rs5219 (KCNJ11 c.67G4A p.Glu23Lys) rs1169288 (HNF1A c.79A4C p.Ile27Leu) rs1169305 (HNF1A c.1720A4G p.Ser574Gly) rs1260326 (GCKR c.1403C4T p.Pro446Leu) rs3856806 (PPARG c.1347C4 T p.His449His) rs100010131 (WFS1 IVS4-9G4A) rs5219 rs1169288 rs1169305 rs1260326 rs100010131 rs5219 rs1169288 rs1169305 rs1260326 rs3856806 rs100010131 RFX6 (c.1558A4T p.Ser520Thr) inherited from the mother ABCC8 (c.4500C4A p.Ser1500Arg) inherited from the father Abbreviations: NA, not available; SNP, single-nucleotide polymorphisms. Login to comment