ABCMdb

ABCC8 p.Leu511Met

Predicted by SNAP2:	A: N (53%), C: N (82%), D: D (75%), E: D (66%), F: N (72%), G: D (66%), H: D (63%), I: N (61%), K: D (71%), M: N (82%), N: D (66%), P: D (75%), Q: D (59%), R: D (66%), S: N (53%), T: D (53%), V: N (61%), W: D (59%), Y: N (53%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, 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
104 1 DPET htzP Flanagan et al, 200817 ABCC8 Exon 8 c.1177-?_1332+?del p.Thr393_Gln444del52 1 DH c-htz This report ABCC8 Exon 8 c.1331A/G p.Gln444Arg 1 FH Damaj et al, 200845 ABCC8 Exon 10 c.1508T/C p.Leu503Pro 1 FH Flanagan et al, 200817 ABCC8 Exon 10 c.1531C/A p.Leu511Met 2 DH htz, htznovo This report ABCC8 Intron 10 c.1630+1G/T p.? Login to comment
107 1 DH c-htz This report ABCC8 Exon 16 c.2124_2127delGACT p.Thr709X 1 FH This report ABCC8 Exon 16 c.2147G/A p.Gly716Asp 1 DPET htzm This report ABCC8 Exon 16 c.2153delG p.Gly718fs 1 DH htzP This report ABCC8 Exon 20 c.2425C/T p.Gln809X 1 DH c-htz Damaj et al, 200845 ABCC8 Exon 20 c.2473G/A p.Glu825Lys 1 DPET htzP This report ABCC8 Exon 22 c.2560-?_2697+?del p.Asp854_Trp899del46 1 DH c-htz This report ABCC8 Exon 22 c.2581G/C p.Asp861His 1 DPVS c-htz This report ABCC8 Exon 22 c.2669A/C p.Lys890Thr 1 DH htzP Flanagan et al, 200817 ABCC8 Exon 22 c.2672T/C p.Leu891Pro 1 DH htznovo This report ABCC8 Exon 23 c.2702T/C p.Ile901Thr 2 DH, DPET c-htz This report ABCC8 Exon 23 c.2784G/A p.Trp928X 1 FH This report ABCC8 Exon 23 c.2803C/T p.Gln935X 1 DPET c-htz This report ABCC8 Exon 24 c.2860C/T p.Gln954X 1 FH Flanagan et al, 200817 ABCC8 Intron 24 c.2924-9G/A p.? Login to comment