ABCMdb

ABCC8 p.Leu580Phe

Predicted by SNAP2:	A: D (63%), C: D (53%), D: D (91%), E: D (85%), F: D (71%), G: D (85%), H: D (80%), I: N (66%), K: D (85%), M: N (66%), N: D (80%), P: D (85%), Q: D (75%), R: D (85%), S: D (80%), T: D (66%), V: N (61%), W: D (80%), Y: D (63%),
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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No. Sentence Comment
105 3 FH (x2), DPET htzP Flanagan et al, 2008 ABCC8 Exon 12 c.1732_1746dup15 p.Ala578_Leu582dup5 1 DPET htzP Flanagan et al, 200817 ABCC8 Exon 12 c.1738C/T p.Leu580Phe 1 DPET hmz This report ABCC8 Exon 12 c.1792C/T p.Arg598X 2 FH, DH c-htz Flanagan et al, 200817 ABCC8 Intron 13 c.1923+5G/T p.? Login to comment
108 3 FH (x2), DPET htzP Flanagan et al, 2008 ABCC8 Exon 12 c.1732_1746dup15 p.Ala578_Leu582dup5 1 DPET htzP Flanagan et al, 200817 ABCC8 Exon 12 c.1738C/T p.Leu580Phe 1 DPET hmz This report ABCC8 Exon 12 c.1792C/T p.Arg598X 2 FH, DH c-htz Flanagan et al, 200817 ABCC8 Intron 13 c.1923+5G/T p.? Login to comment