The Tier 1 Hyperinsulinism Panel for Diazoxide-Unresponsive Hyperinsulinism is designed for critically ill newborns and infants in whom rapid molecular diagnosis is essential for immediate treatment and management decisions. This assay provides results in less than 7 days and focuses on the highest-yield genetic causes of diazoxide-unresponsive hyperinsulinism, including sequencing of ABCC8, KCNJ11, GCK, and the recently recognized pathogenic non-coding cis-regulatory region within intron 2 of HK1. The panel also includes deletion/duplication analysis of ABCC8 and the HK1 regulatory region by MLPA. Early identification of a genetic etiology can help distinguish individuals who may respond to diazoxide therapy from those more likely to require surgical intervention for focal or diffuse disease. The inclusion of the HK1 regulatory region expands detection beyond traditional coding variants and improves identification of important non-coding causes of congenital hyperinsulinism.
Test Methodology:
Testing is performed using Sanger sequencing of all coding exons and intron/exon boundaries of ABCC8, KCNJ11, and GCK, along with targeted sequencing of the HK1 intron 2 regulatory region. The assay also includes analysis of the deep intronic pathogenic splice variants ABCC8 c.3989-9G>A and c.1333-1013A>G. Deletion/duplication analysis of ABCC8 and the HK1 intronic targeted region is performed by MLPA.
Because interpretation of variants identified in these genes often depends on inheritance pattern, parental samples are strongly recommended and should ideally be submitted with the proband sample. Please contact the lab when sending the sample/s so we confirm its receipt.
Also available is our comprehensive NGS-based Hyperinsulinism Panel for broader evaluation of genetically heterogeneous forms of hyperinsulinism.
