Table 1.
Mutations identified by targeted next-generation sequencinga
| Gene | RefSeq | Mutation(s) by nucleotide | Mutation(s) by amino acid | Mutation type | Zygosity | Patient phenotype | Method of detection |
|---|---|---|---|---|---|---|---|
| ABCC8 | U63421 and L78208 | c.4261C>T+c.4594A>G | p.R1421C+p.T1532A | Base substitutions | Compound heterozygous | Hyperinsulinism | Sanger sequencing |
| ABCC8 | U63421 and L78208 | c.1631T>C+c.3643C>T | p.I544R+p.R1215W | Base substitutions | Compound heterozygous | Neonatal diabetes | Sanger sequencing |
| ABCC8 | U63421 and L78208 | c.1333-2374_1671+121dup | Duplication of exons 9–11 | Heterozygous | Hyperinsulinism | MLPA | |
| ABCC8 | U63421 and L78208 | c.580-1G>C+c.2476C>T | p.R826W | Base substitutions | Compound heterozygous | Neonatal diabetes | Next-generation sequencing |
| CEL | NM_001807.3 | c.1742_2170del | Small indel | Heterozygous | MODY | Sanger sequencing | |
| CEL | NM_001807.3 | c.1686delT | Small indel | Heterozygous | MODY | Sanger sequencing | |
| CEL | NM_001807.3 | c.1785delC | Small indel | Heterozygous | MODY | Sanger sequencing | |
| EIF2AK3 | AF110146.1 | c.2304_2305delTG | Small indel | Homozygous | Neonatal diabetes | Sanger sequencing | |
| EIF2AK3 | AF110146.1 | c.818delC | Small indel | Homozygous | Neonatal diabetes | Sanger sequencing | |
| EIF2AK3 | AF110146.1 | c.1894C>T | p.R632W | Base substitution | Homozygous | Neonatal diabetes | Next-generation sequencing |
| EIF2AK3 | AF110146.1 | c.3029G>A | p.G1010D | Base substitution | Heterozygous | Unaffected parent | Sanger sequencing |
| FOXP3 | NM_014009.2 | c.1234_1260del27 | Small indel | Hemizygous | Neonatal diabetes | Sanger sequencing | |
| FOXP3 | NM_014009.2 | c.1010G>A | p.R339Q | Base substitution | Hemizygous | Neonatal diabetes | Sanger sequencing |
| GATA6 | NM_005257.3 | c.1354A>AG; p.T452A | p.T452A | Base substitution | Heterozygous | Neonatal diabetes | Sanger sequencing |
| GATA6 | NM_005257.3 | c.1448_1455delTGAAAAAA | Small indel | Heterozygous | Neonatal diabetes | Sanger sequencing | |
| GATA6 | NM_005257.3 | c.1296del | Small indel | Heterozygous | Neonatal diabetes | Next-generation sequencing | |
| GATA6 | NM_005257.3 | c.1397A>G | p.N466S | Base substitution | Heterozygous | Neonatal diabetes | Next-generation sequencing |
| GATA6 | NM_005257.3 | c.1303-1G>T | Base substitution | Mosaic | Unaffected parent | Sanger sequencing | |
| GCK | NM_000162.2 | IVS4+2_+16del15 | Small indel | Heterozygous | MODY | Sanger sequencing | |
| GCK | NM_000162.2 | c.544G>A | p.V182M | Base substitution | Heterozygous | MODY | Sanger sequencing |
| GCK | NM_000162.2 | c.1-?_45+?del | Deletion of exon 1 | Heterozygous | MODY | MLPA | |
| GCK | NM_000162.2 | c.764_767dup | Small indel | Homozygous | Neonatal diabetes | Next-generation sequencing | |
| GCK | NM_000162.2 | c.127C>T | p.R43C | Base substitution | Homozygous | Neonatal diabetes | Next-generation sequencing |
| GCK | NM_000162.2 | c.458C>A | p.P153H | Base substitution | Heterozygous | MODY | Next-generation sequencing |
| GCK | NM_000162.2 | c.-557G>C | Base substitution | Heterozygous | MODY | Sanger sequencing | |
| GLIS3 | NM_001042413.1 | c.1765C>T+c.1-?_2790+?del | p.R589W | Base substitution+ deletion of exons 2–11 | Compound heterozygous | Neonatal diabetes | Sanger sequencing and array CGH |
| HNF1A | NM_000545.3 | c.872dup | Small indel | Heterozygous | MODY | Sanger sequencing | |
| HNF1A | NM_000545.3 | c.1502-6G>A | Base substitution | Heterozygous | MODY | Sanger sequencing | |
| HNF1B | NM_000458.1 | c.1-?_1674+?del | Deletion of exons 1–9 | Heterozygous | RCAD | MLPA | |
| HNF1B | NM_000458.1 | c.466A>G | p.K156E | Base substitution | Heterozygous | RCAD | Sanger sequencing |
| HNF1B | NM_000458.1 | c.810-344_c.1207-2413dup | Duplication of exons 4–5 | Heterozygous | RCAD | MLPA | |
| HNF1B | NM_000458.1 | c.475C>G | p.P159A | Base substitution | Heterozygous | MODY | Next-generation sequencing |
| HNF4A | LRG_483 | c.940A>T | p.I314F | Base substitution | Heterozygous | MODY | Sanger sequencing |
| HNF4A | LRG_483 | c.358+5G>A | Base substitution | Heterozygous | MODY | Next-generation sequencing | |
| IER3IP1 | NM_010697.3 | c.235T>C | c.L78P | Base substitution | Homozygous | Neonatal diabetes | Sanger sequencing |
| INS | NM_000207.2 | c.94G>T | p.32C | Base substitution | Heterozygous | Neonatal diabetes | Sanger sequencing |
| INS | NM_000207.2 | c.265C>T | p.R89C | Base substitution | Heterozygous | Neonatal diabetes | Sanger sequencing |
| KCNJ11 | NM_000525.3 | c.602G>A | p.R201H | Base substitution | Heterozygous | Neonatal diabetes | Sanger sequencing |
| Mitochondrial | NC_012920.1 | m.3243A>G | Base substitution | Heteroplasmic | MODY | Next-generation sequencing | |
| Mitochondrial | NC_012920.1 | m.3243A>G | Base substitution | Heteroplasmic | MODY | Next-generation sequencing | |
| NKX2-2 | NM_002509.3 | c.365delC | Small indel | Homozygous | Neonatal diabetes | Sanger sequencing | |
| PDX1 | NM_000209.1 | c.54C>A | p.C18X | Base substitution | Heterozygous | Neonatal diabetes | Sanger sequencing |
| PDX1 | NM_000209.1 | c.508T>C | p.Y170H | Base substitution | Homozygous | Neonatal diabetes | Next-generation sequencing |
| SLC19A2 | NM_006996.2 | c.759dup | Base substitution | Homozygous | Neonatal diabetes | Next-generation sequencing | |
| SLC19A2 | NM_006996.2 | c.958T>G | p.W320G | Base substitution | Homozygous | Neonatal diabetes | Next-generation sequencing |
| WFS1 | NM_006005.3 | c.2489A>C | p.E830A | Base substitution | Heterozygous | Neonatal diabetes | Sanger sequencing |
aThese included the 34 mutations in 32 positive control samples identified previously by Sanger sequencing, MLPA or array CGH and the newly discovered mutations in 14 patients in whom previous genetic testing for neonatal diabetes or MODY had not identified a monogenic cause for their diabetes