ABCC8 p.Trp739Cys
| Predicted by SNAP2: | A: D (63%), C: D (53%), D: D (85%), E: D (71%), F: N (53%), G: D (66%), H: N (57%), I: N (66%), K: D (75%), L: N (61%), M: N (72%), N: D (66%), P: D (91%), Q: D (63%), R: D (63%), S: D (59%), T: N (53%), V: N (61%), Y: N (53%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: 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, Y: D, |
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[hide] A novel case of compound heterozygous congenital h... Int J Pediatr Endocrinol. 2015;2015(1):16. doi: 10.1186/s13633-015-0012-4. Epub 2015 Jul 15. Brady C, Palladino AA, Gutmark-Little I
A novel case of compound heterozygous congenital hyperinsulinism without high insulin levels.
Int J Pediatr Endocrinol. 2015;2015(1):16. doi: 10.1186/s13633-015-0012-4. Epub 2015 Jul 15., [PMID:26180531]
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BACKGROUND: Congenital hyperinsulinism leads to unregulated insulin secretion and hypoglycemia. Diagnosis can be difficult and genetic testing may be warranted. CASE: This patient initially presented at 11 months with seizure activity secondary to severe hypoglycemia. Her diagnostic evaluation included genetic studies, which confirmed congenital hyperinsulinism. A novel combination of mutations in the ABCC8 gene leading to diffuse, diazoxide-unresponsive congenital hyperinsulinism was identified. Mutation analysis of ABCC8 showed three variants (R1215W - paternal, pathogenic; W739C - maternal, variant of unknown significance; R1393L - maternal, variant of unknown significance). Her clinical course continues to be complicated by severe, refractory hypoglycemia at age 3 years. CONCLUSION: We describe a novel compound heterozygous mutation leading to diffuse, diazoxide-unresponsive congenital hyperinsulinism. This case illustrates challenges associated with diagnosing and managing congenital hyperinsulinism and the importance of genetic testing.
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No. Sentence Comment
5 Mutation analysis of ABCC8 showed three variants (R1215W - paternal, pathogenic; W739C - maternal, variant of unknown significance; R1393L - maternal, variant of unknown significance).
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ABCC8 p.Trp739Cys 26180531:5:81
status: NEW59 The R1215W variant was found to be paternally-inherited while the W739C and R1393L variants were maternally inherited.
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ABCC8 p.Trp739Cys 26180531:59:66
status: NEW62 In our patient, the significance of the maternal variants was unclear as they had not been previously described in Table 1 Fasting challenge results Test name (Normal range) Laboratory result IGFBP-1 (ng/mL) (5-9 years: 15-95; no reference range for patients <5 years) 61 Insulin (<2-13 bc;IU/mL fasting) 0.2 Glucose (>70 mg/dL/3.885 mmol/L) 32/1.776 C-peptide (0.8-3.5 ng/mL) 0.5 BOHB (0-3.0 mg/dL) 4.3 (0.41 mmol/L) Free Fatty Acids (0.5-0.9 mmol/L) 0.46 Growth Hormone (>7 ng/mL) 3 Table 2 Genetic results (ABCC8 Mutation) Mutation Inheritance Interpretation c. R1215W Paternal Pathogenic c. W739C Maternal VUS c. R1393L Maternal VUS VUS variant of unknown significance CHI cases.
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ABCC8 p.Trp739Cys 26180531:62:598
status: NEW114 We have recently learned (from a patient at Children`s Hospital of Philadelphia) that the W739C maternal variant has been identified in a patient with diffuse disease indicating that it likely acts recessively.
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ABCC8 p.Trp739Cys 26180531:114:90
status: NEW