ABCC8 p.Arg521Pro
| ClinVar: |
c.1562G>A
,
p.Arg521Gln
?
, Uncertain significance
|
| Predicted by SNAP2: | A: N (66%), C: N (53%), D: D (59%), E: N (57%), F: D (66%), G: D (53%), H: N (78%), I: N (57%), K: N (97%), L: N (57%), M: N (53%), N: N (72%), P: D (59%), Q: N (82%), S: N (82%), T: N (72%), V: N (57%), W: D (66%), Y: D (66%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, S: N, T: N, V: N, W: D, Y: N, |
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[hide] The contribution of rapid KATP channel gene mutati... Eur J Endocrinol. 2011 May;164(5):733-40. Epub 2011 Mar 4. Banerjee I, Skae M, Flanagan SE, Rigby L, Patel L, Didi M, Blair J, Ehtisham S, Ellard S, Cosgrove KE, Dunne MJ, Clayton PE
The contribution of rapid KATP channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism.
Eur J Endocrinol. 2011 May;164(5):733-40. Epub 2011 Mar 4., [PMID:21378087]
Abstract [show]
OBJECTIVE: In children with congenital hyperinsulinism (CHI), K(ATP) channel genes (ABCC8 and KCNJ11) can be screened rapidly for potential pathogenic mutations. We aimed to assess the contribution of rapid genetic testing to the clinical management of CHI. DESIGN: Follow-up observational study at two CHI referral hospitals. METHODS: Clinical outcomes such as subtotal pancreatectomy, (18)F-Dopa positron emission tomography-computed tomography (PET-CT) scanning, stability on medical treatment and remission were assessed in a cohort of 101 children with CHI. RESULTS: In total, 32 (32%) children had pathogenic mutations in K(ATP) channel genes (27 in ABCC8 and five in KCNJ11), of which 11 (34%) were novel. In those negative at initial screening, other mutations (GLUD1, GCK, and HNF4A) were identified in three children. Those with homozygous/compound heterozygous ABCC8/KCNJ11 mutations were more likely to require a subtotal pancreatectomy CHI (7/10, 70%). Those with paternal heterozygous mutations were investigated with (18)F-Dopa PET-CT scanning and 7/13 (54%) had a focal lesionectomy, whereas four (31%) required subtotal pancreatectomy for diffuse CHI. Those with maternal heterozygous mutations were most likely to achieve remission (5/5, 100%). In 66 with no identified mutation, 43 (65%) achieved remission, 22 (33%) were stable on medical treatment and only one child required a subtotal pancreatectomy. CONCLUSIONS: Rapid genetic analysis is important in the management pathway of CHI; it provides aetiological confirmation of the diagnosis, indicates the likely need for a subtotal pancreatectomy and identifies those who require (18)F-Dopa PET-CT scanning. In the absence of a mutation, reassurance of a favourable outcome can be given early in the course of CHI.
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No. Sentence Comment
63 Patient Gene Mutation (nucleotide) Mutation (protein) Inheritance Response to diazoxide #1 ABCC8 Exon 1 c.107AOG p.His36Arg Compound heterozygote: maternal and paternal U #2 ABCC8 Exon 1 c.11COT p.Ala4Val Presumed paternal compound heterozygote U #3 ABCC8 Exon 2 c.208GOA p.Gly70Arg Compound heterozygote: maternal and paternal U #4 ABCC8 Exon 37 c.4547COT p.Thr1516Met Heterozygous maternal R #5 ABCC8 Exon 34 c.4169TOG p.Leu1390Arg De novo R #6 ABCC8 Exon 10 Exon 33 c.1562GOC and c.4079COT p.Arg521Pro p.Pro1360Leu Compound heterozygote: maternal and paternal U #7 ABCC8 Exon 21 c.2525GOA p.Arg842Gln Paternal heterozygote U #8 ABCC8 Intron 9 c.1467C5GOA p.?
X
ABCC8 p.Arg521Pro 21378087:63:495
status: NEW