ABCMdb

PMID: 21049026

Bonnefond A, Durand E, Sand O, De Graeve F, Gallina S, Busiah K, Lobbens S, Simon A, Bellanne-Chantelot C, Letourneau L, Scharfmann R, Delplanque J, Sladek R, Polak M, Vaxillaire M, Froguel P
Molecular diagnosis of neonatal diabetes mellitus using next-generation sequencing of the whole exome.
PLoS One. 2010 Oct 26;5(10):e13630., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC8 p.Gln485His From our WES with high-quality reads, we identified a novel non-synonymous mutation in ABCC8 (c.1455G.C/p.Q485H), despite a previous negative sequencing of this gene. Login to comment 57 ABCC8 p.Gln485His Unexpectedly, we identified a novel heterozygous non-synonymous mutation c.1455G.C/p.Q485H in the 9th exon of ABCC8. Login to comment 59 ABCC8 p.Gln485His ABCC8 p.Gln485His Unexpectedly, we identified a novel heterozygous non-synonymous mutation c.1455G.C/p.Q485H in the 9th exon of ABCC8. Login to comment 60 ABCC8 p.Gln485His In addition, retrospective re-examination of the data generated six years ago indicated that the p.Q485H mutation was present in the original ABCC8 exon 9 sequences (chromogram). Login to comment 61 ABCC8 p.Gln485His ABCC8 p.Gln485His In both cases, we identified the p.Q485H mutation in ABCC8, confirming our WES results. Login to comment 62 ABCC8 p.Gln485His ABCC8 p.Gln485His In addition, retrospective re-examination of the data generated six years ago indicated that the p.Q485H mutation was present in the original ABCC8 exon 9 sequences (chromogram). Login to comment 63 ABCC8 p.Gln485His The ABCC8 p.Q485H mutation was not found in 348 French nondiabetic individuals or in the patient`s mother, father and young brother, all of whom are normoglycemic. Login to comment 64 ABCC8 p.Gln485His ABCC8 p.Gln485His ABCC8 p.Gln485His The p.Q485H mutation affects an amino acid that is located in the transmembrane domain 1 (TMD1) of the ABCC8/SUR1 core; and that is highly conserved across species (Rhesus, Mouse, Dog, Rabbit, Elephant, Opossum, Platypus, Chicken, Lizard, Stickleback, X_Tropicalis, Tetraodon) according to the UCSC (NCBI/hg18) comparative genomics alignment pipeline (http://www.bx.psu. Login to comment 66 ABCC8 p.Gln485His ABCC8 p.Gln485His We evaluated the possible functional significance of the p.Q485H mutation by the PolyPhen-2 (Polymorphism Phenotyping v2) software which uses sequenceand structure-based criteria to predict the putative impact of point mutations on the structure and function of human proteins [8]: the p.Q485H mutation is predicted 'probably damaging` with a score of 0.999 (the score of 1 indicating the most damaging mutation). Login to comment 76 ABCC8 p.Gln485His The p.Q485H mutation was missed six years ago by the research assistant in charge of the sequence reading. Login to comment 78 ABCC8 p.Gln485His The p.Q485H mutation was missed six years ago by the research assistant in charge of the sequence reading. Login to comment 85 ABCC8 p.Gln485His We are quite confident that the p.Q485H mutation is likely to be functional given the non ambiguous prediction of its putative damaging effect. Login to comment 87 ABCC8 p.Gln485His We are quite confident that the p.Q485H mutation is likely to be functional given the non ambiguous prediction of its putative damaging effect. Login to comment 112 ABCC8 p.Gln485His Mutation validation The p.Q485H mutation identified via WES was confirmed using the Sanger method. Login to comment 114 ABCC8 p.Gln485His Mutation validation The p.Q485H mutation identified via WES was confirmed using the Sanger method. Login to comment