ABCMdb

ABCC8 p.Gly684Glu

Predicted by SNAP2:	A: N (66%), C: D (66%), D: D (71%), E: D (80%), F: D (80%), H: D (75%), I: D (75%), K: D (80%), L: D (75%), M: D (75%), N: D (63%), P: D (85%), Q: D (75%), R: D (85%), S: D (59%), T: D (63%), V: D (71%), W: D (80%), Y: D (80%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] ABCC8 and KCNJ11 molecular spectrum of 109 patient... J Med Genet. 2010 Nov;47(11):752-9. Epub 2010 Aug 3. Bellanne-Chantelot C, Saint-Martin C, Ribeiro MJ, Vaury C, Verkarre V, Arnoux JB, Valayannopoulos V, Gobrecht S, Sempoux C, Rahier J, Fournet JC, Jaubert F, Aigrain Y, Nihoul-Fekete C, de Lonlay P
ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.
J Med Genet. 2010 Nov;47(11):752-9. Epub 2010 Aug 3., [PMID:20685672]

Abstract [show]
BACKGROUND: Congenital hyperinsulinism (CHI) is characterised by an over secretion of insulin by the pancreatic beta-cells. This condition is mostly caused by mutations in ABCC8 or KCNJ11 genes encoding the SUR1 and KIR6.2 subunits of the ATP-sensitive potassium (K(ATP)) channel. CHI patients are classified according to their responsiveness to diazoxide and to their histopathological diagnosis (either focal, diffuse or atypical forms). Here, we raise the benefits/limits of the genetic diagnosis in the clinical management of CHI patients. METHODS: ABCC8/KCNJ11 mutational spectrum was established in 109 diazoxide-unresponsive CHI patients for whom an appropriate clinical management is essential to prevent brain damage. Relationships between genotype and radiopathological diagnosis were analysed. RESULTS: ABCC8 or KCNJ11 defects were found in 82% of the CHI cases. All patients with a focal form were associated with a single K(ATP) channel molecular event. In contrast, patients with diffuse forms were genetically more heterogeneous: 47% were associated with recessively inherited mutations, 34% carried a single heterozygous mutation and 19% had no mutation. There appeared to be a predominance of paternally inherited mutations in patients diagnosed with a diffuse form and carrying a sole K(ATP) channel mutation. CONCLUSIONS: The identification of recessively inherited mutations related to severe and diffuse forms of CHI provides an informative genetic diagnosis and allows prenatal diagnosis. In contrast, in patients carrying a single K(ATP) channel mutation, genetic analysis should be confronted with the PET imaging to categorise patients as focal or diffuse forms in order to get the appropriate therapeutic management.

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Sentences [show]
No. Sentence Comment
106 1 FH This report ABCC8 Exon 14 c.2035_2036insCTGT p.Val679fs 1 DH hmz This report ABCC8 Exon 15 c.2051G/A p.Gly684Glu 1 FH This report ABCC8 Exon 15 c.2064G/A p.Trp688X 1 FH Giurgea et al, 200446 ABCC8 Intron 15 c.2116+2T/C p.? Login to comment
109 1 FH This report ABCC8 Exon 14 c.2035_2036insCTGT p.Val679fs 1 DH hmz This report ABCC8 Exon 15 c.2051G/A p.Gly684Glu 1 FH This report ABCC8 Exon 15 c.2064G/A p.Trp688X 1 FH Giurgea et al, 200446 ABCC8 Intron 15 c.2116+2T/C p.? Login to comment