Table 1.

Known genetic causes of isolated congenital hyperinsulinism and current approaches to genetic testing for this condition. A tick (✓) or cross (X) denote whether the form of genetic variation can be detected by the screening approach. None of the variants listed will be detected by methylation studies or array-CGH analysis. SNVs are single nucleotide variants, Indels are insertion/deletion variants and CNVs are copy number variants (deletions and duplications).

Gene	Zygosity	Mutation type	SangerSequencing1	Next Generation Sequencing			Ref
				Targeted Panel	Exome	Genome
ABCC8	Dominant or recessive	SNVs/indels	✓	✓	✓2	✓	(8–10)
		Large CNVs	X	✓	✓	✓
GCK	Dominant	SNVs/indels	✓	✓	✓	✓	(11)
GLUD1	Dominant	SNVs/indels	✓	✓	✓	✓	(12)
HADH	Recessive	SNVs/indels	✓	✓	✓2	✓	(13)
		Large CNVs	X	✓	✓	✓	(14)
HK1	Dominant	SNVs/indels	✓	✓	X	✓	(15)
		Large CNVs	X	✓	X	✓
HNF1A	Dominant	SNVs/indels	✓	✓	✓	✓	(16)
HNF4A	Dominant	SNVs/indels	✓	✓	✓2	✓	(17)
		Large CNVs	X	✓	✓	✓	(18)
INSR	Dominant	SNVs/indels	✓	✓	✓	✓	(19)
KCNJ11	Dominant or recessive	SNVs/indels	✓	✓	✓	✓	(20)
SLC16A1	Dominant	SNVs/indels	✓	✓	X	✓	(21)

¹ Sanger sequencing will not detect heterozygous deletions of duplications that extend beyond the targeted region. Homozygous deletions that encompass a primer binding site may be detected by a failure to amplify the sequence, but this will require verification by an independent method.

² Exome sequencing will not detect the deep intronic mutations or promoter mutations reported in these genes (22).