Table 5. PVOD/PCH mutations identified in EIF2AK4.
| Location | Mutation category | Nucleotide change | Amino acid change | Frequency in this study | Clinical classification | Reference(s) |
|---|---|---|---|---|---|---|
| Exon 3; Intron 9 | Frameshift; Splice-site | c.354 355delTG; c.1554-4C>A | p.C118Wfs*7; p.C519Dfs*17 | 1 | PVOD-F | Eyries et al., 2014 |
| Exon 5 | Frameshift | c.560_564delAAGAA; c.560 564delAAGAA | p.K187Rfs*9; p.K187Rfs*9 | 1 | PVOD-S | Eyries et al., 2014 |
| Exon 5 | Frameshift | c.567dupG; c.567dupG | p.K190Efs*8; p.K190Efs*8 | 1 | PVOD-F | Eyries et al., 2014 |
| Exon 7; Exon 12 | Nonsense; Frameshift | c.745C>T; c.2136 2139dupCACT | p.R249*; p.S714Hfs*21 | 1 | PVOD-F | Eyries et al., 2014 |
| Intron 7; Exon 25 | Splice-site; Nonsense | c.860-1G>A; c.3448C>T | p.?; p.R1150* | 1 | PCH | Best et al., 2014 |
| Exon 9; Exon 28 | Frameshift; Nonsense | c.1153dupG; c.3766C>T | p.V385Gfs*30; p.R1256* | 1 | PCH | Best et al., 2014 |
| Exon 9 | Nonsense | c.1387c>t; c.1387c>t | p.R463*; p.R463* | 1 | PVOD-F | Eyries et al., 2014 |
| Exon 9; Exon 23 | Nonsense; Nonsense | c.1387C>T; c.3244C>T | p.R463*; p.Q1082* | 1 | PVOD-F | Eyries et al., 2014 |
| Exon 9 | Frameshift | c.1392delT; c.1392delT | p.R465Vfs*38; p.R465Vfs*38 | 1 | PCH | Best et al., 2014 |
| Exon 9; Exon 28 | Frameshift; Nonsense | c.1392delT; c.3802C>T | p.R465Vfs*38; p.Q1268* | 1 | PVOD-F | Eyries et al., 2014 |
| Exon 11 | Missense | c.1754g>a; c.1754g>a | p.R585Q; p.R585Q | 1 | PVOD-F | Eyries et al., 2014 |
| Exon 12 | Missense | c.1928t>g; c.1928t>g | p.L643R; p.L643R | 1 | PVOD-F | Eyries et al., 2014 |
| Intron 13 | Splice-site | c.2319+1G>A; c.2319+1G>A | p.?; p.? | 1 | PVOD-F | Eyries et al., 2014 |
| Exon 15 | Nonsense | c.2458C>T; c.2458C>T | p.R820*; p.R820* | 1 | PVOD-S | Eyries et al., 2014 |
| Exon 19; Intron 25 | Nonsense; Splice-site | c.2857C>T; c.3576+1G>T | p.Q953*; p.? | 1 | PVOD-S | Eyries et al., 2014 |
| Exon 21 | Splice-site | c.3159G>A; c.3159G>A | p.K975 K1053del; p.K975 K1053del | 2 | PVOD-F, -S | Eyries et al., 2014 |
| Exon 23 | Missense | c.3344C>T; c.3344C>T | p.P1115L; p.P1115L | 5 | H | Tenorio et al., 2014 |
| Exon 24 | Nonsense | c.3406C>T; c.3406C>T | p.R1136*; p.R1136* | 1 | PVOD-F | Eyries et al., 2014 |
| Exon 25; Intron 36 | Nonsense; Splice-site | c.3448C>T; c.4728+1 4728+13delinsTTCT | p.R1150*; p.? | 1 | PVOD-F | Eyries et al., 2014 |
| Intron 29 | Splice-site | c.4065+1G>C; c.4065+1G>C | p.?; p.? | 1 | PVOD-F | Eyries et al., 2014 |
| Exon 31 | Frameshift | c.4205dupT; c.4205dupT | p.S1403Kfs*45; p.S1403Kfs*45 | 1 | PVOD-S | Eyries et al., 2014 |
†
GenBank reference sequence and version number for EIF2AK4: NM_001013703.3
‡
Total number of independent cases
Key to abbreviations: H: heritable pulmonary arterial hypertension; PCH: pulmonary capillary hemangiomatosis; PVOD: pulmonary veno-occlusive disease (-F: familial; -S: sporadic)