ABCMdb

PMID: 22306677

Mak CM, Lee CY, Lam CW, Siu WK, Hung VC, Chan AY
Personalized medicine switching from insulin to sulfonylurea in permanent neonatal diabetes mellitus dictated by a novel activating ABCC8 mutation.
Diagn Mol Pathol. 2012 Mar;21(1):56-9., [PubMed]

Sentences

No. Mutations Sentence Comment

8 ABCC8 p.His1023Arg Results: A novel homozygous ABCC8 NM_000352.3: c.3068A>G; NP_000343.2: p.H1023R mutation was detected. Login to comment 33 ABCC8 p.Val86Ala The last patient carried a heterozygous mutation (p.V86A) in ABCC8 with baseline C-peptide of 0.003nmol/L and initially required insulin of 0.45 IU/kg/d. Login to comment 68 ABCC8 p.His1023Arg RESULTS AND DISCUSSIONS We characterized a novel homozygous mutation ABCC8 NM_000352.3: c.3068 A>G; NP_000343.2: p.H1023R in this Chinese patient with permanent NDM (Fig. Login to comment 71 ABCC8 p.His1023Arg The parents were obligatory heterozygous carrier and healthy. The maternal grandparents who were in their 70s were also healthy. The treatment outcome by sulfonylurea was satisfactory in our patient harboring homozygous p.H1023R. Login to comment 90 ABCC8 p.His1023Arg A novel homozygous mutation in ABCC8 NM_ 000352.3: c.3068A>G; NP_000343.2: p.H1023R was identified in our Chinese patient with permanent NDM. Login to comment 91 ABCC8 p.His1023Tyr Another activating mutation at the same amino acid with substitution by tyrosine (p.H1023Y) was reported by Babenko et al12 in 2006. Login to comment 92 ABCC8 p.His1023Tyr Their patient, who harbored a de novo heterozygous p.H1023Y, presented with transient NDM with hyperglycemia of 37.8mmol/L and diabetic ketoacidosis at the age of 21 days. Login to comment 95 ABCC8 p.His1023Tyr The investigators had screened for more than 300 individuals and p.H1023Y was not seen in any individuals. Login to comment 96 ABCC8 p.His1023Tyr Babenko et al. also confirmed the pathogenicity of p.H1023Y by electrophysiological analysis of the KATP-channel. Login to comment 97 ABCC8 p.His1023Tyr Mutant p.H1023Y showed an overreactive channel, which remains sensitive to sulfonylurea. Login to comment 100 ABCC8 p.His1023Arg ABCC8 p.His1023Arg Conceivably, p.H1023R detected in our patient likely explains her permanent condition of NDM. Interestingly, heterozygous carriers of p.H1023R (the patient`s parents and either one of her maternal grandparents) did not have any form of diabetes mellitus documented so far. Login to comment 101 ABCC8 p.His1023Arg We postulate that the homozygous p.H1023R contributes for a synergistic effect, resulting in a more severe phenotype of permanent NDM instead of the transient form. Login to comment 108 ABCC8 p.His1023Arg Recommendation regarding the potential risk of late-onset diabetes mellitus was also given to the parents being heterozygous for p.H1023R during the posttest genetic counseling. Login to comment 113 ABCC8 p.His1023Arg A novel homozygous mutation ABCC8 NM_000352.3: c.3068A>G; NP_000343.2: p.H1023R was identified in our Chinese patient with permanent NDM (in the sense direction). Login to comment