ABCMdb

ABCC8 p.His1023Arg

Predicted by SNAP2:	A: D (53%), C: D (66%), D: D (59%), E: D (66%), F: D (71%), G: N (61%), I: D (66%), K: D (59%), L: D (75%), M: D (63%), N: N (78%), P: D (80%), Q: N (82%), R: D (71%), S: N (72%), T: D (63%), V: D (66%), W: D (80%), Y: D (71%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, I: D, K: D, L: D, M: D, N: N, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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[hide] Personalized medicine switching from insulin to su... Diagn Mol Pathol. 2012 Mar;21(1):56-9. 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., [PMID:22306677]

Abstract [show]
BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare but important condition affecting approximately 1 in 100,000 newborns. Permanent form requires life-long treatment with difficulties in long-term compliance and metabolic complications. Exact genetic diagnosis can enable improved outcome and patient satisfaction by switching insulin injection to oral sulfonylureas. Successful cases have been reported with most experience on the KCNJ11-mutated permanent form. Here we report a successful experience in an ABCC8-mutated infant with permanent NDM. PATIENT AND METHODS: A 4-month-old Chinese girl was incidentally found to have hyperglycemia with baseline C-peptide of 0.05 nmol/L requiring insulin injection of 0.2 IU/kg/d. Genetic analysis of KCNJ11 and ABCC8 was performed by polymerase chain reaction and direct DNA sequencing at the age of 3 years. Sulfonylurea transition was conducted after the ABCC8 mutation detection. RESULTS: A novel homozygous ABCC8 NM_000352.3: c.3068 A>G; NP_000343.2: p.H1023R mutation was detected. C-peptide level increased to 0.14 nmol/L and HbA1c was normalized to 5.8% from 8.0% after 8 months of oral glibenclamide treatment with a maintenance dosage of 0.65 mg/kg/d. CONCLUSIONS: In this patient with ABCC8-mutated permanent NDM, oral sulfonylurea is also effective in achieving satisfactory diabetic control. Our study adds information to the personalized medicine practice of ABCC8-mutated permanent NDM.

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No. Sentence Comment
8 Results: A novel homozygous ABCC8 NM_000352.3: c.3068A>G; NP_000343.2: p.H1023R mutation was detected. Login to comment
68 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 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 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
100 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 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 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 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