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Dryad

Supplemental data from: Next-generation sequencing base calls for mosaic mutations

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Nov 05, 2024 version files 25.29 KB

Abstract

Context: Some children with diazoxide-unresponsive congenital hyperinsulinism (HI) lack any detectable disease-causing mutation in peripheral blood DNA. 

Objective: To examine whether somatic post-zygotic mutations of known HI genes are responsible for disease in children with diazoxide-unresponsive HI requiring surgery with histology not classified as focal or LINE, and without detectable mutations by standard genetic testing of peripheral blood DNA. 

Methods: Next-generation sequencing (NGS) was performed on specimens of pancreas from 10 children with diazoxide-unresponsive HI.

Results: Four unique GCK mutations were identified at low levels of mosaicism ranging from 4.4-10.1% in pancreatic DNA from five of these 10 children.  The GCK mutations were not detectable in peripheral blood DNA by NGS in three cases from which peripheral blood DNA was available for testing.  All four GCK mutations have been previously published as activating HI mutations.     

Conclusion: These results indicate that post-zygotic somatic mutations of known HI genes are responsible for some cases of diazoxide-unresponsive hyperinsulinism.