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

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.