Table 1.
Summary of mutations found in ALDH7A1
| Family | Current age | α-AASA concentration mmol/mol creatinine | Mutation | Presumed effect | Age of onset | Published (ref.) |
|---|---|---|---|---|---|---|
| F1.2 | Died at 1 m | 316(Am) | c.[1482-1G>C] (P) + c.[1482-1G>C] (M) | Splice errors + splice errors | 1 h | Novel |
| F2 | 1 y | 93(Lon), 138(Lon) | c. [248G>A] + c. [818A>T] | p. [Gly83Glu] + p. [Asn273Ile] | 7 d | Plecko et al., 2007; Gallagher et al., 2009 |
| F3 | 14 y, 9 m | 90(Am) | c. [712C>T] + c. [712C>T] | p. [Arg238Stop] + p. [Arg238Stop] | 2 d | Bennett et al., 2009 |
| F4.2 | 3 y, 11 m | 72 (Lon) | c. [758delA] (P) + c. [758delA] (M) | p. [Gln253 frameshift] (P) + p. [Gln253 frameshift] (M) | <24 h | Novel |
| F5 | 2 y, 2 m | 42(Lon) | c. [1195G>C] +c.[1343C>T] | p. [Glu399Gln] + p. [Ser448Leu] | 9 weeks | Mills et al., 2006; novel |
| F6 | 4 y, 10 m | 41 (Lon) | c. [1195G>C] (P) + c. [1195G>C] (M) | p. [Glu399Gln] (P) + p. [Glu399Gln] (M) | 2 h | Mills et al., 2006 |
| F7.1 | 13 y, 10 m | 25 (Lon) | c. [750G>A] (M) + c. [233C>T] (P) | Splice errors (M) + p. [Pro78Leu] (P) | 3 d | Salomons et al., 2007; novel |
| F7.2 | 15 y, 5 m | 12(Lon) | c. [750G>A] (M) + c. [233C>T] (P) | Splice errors (M) + p. [Pro78Leu] (P) | 3 d | Salomons et al., 2007; novel |
| F8 | 4 y, 5 m | 21(Lon) | c.[1195G>C] +? | p. [Glu399Gln] +? | 6 d | Mills et al., 2006 |
| F9 | 6 y, 11 m | 21(Am) | c. [1195G>C] (P) + c. [1195G>C] (M) | p. [Glu399Gln] (P) + p. [Glu399Gln] (M) | <24 h | Mills et al., 2006 |
| F10 | 3 y, 6 m | 14(Lon) | c.191_192insA (M) + c.[1195G>C] (P) | p. [Val64 frameshift] (M) + p. [Glu399Gln] (P) | 2 h | Mills et al., 2006; novel |
| F11.1 | 9 y, 4 m | 11(Am) | c.[750G>A] (P) + c.[505C>T] (M) | Splice errors (P) + p. [Pro169Ser] (M) | 8 d | Salomons et al., 2007; novel |
| F11.2 | 6 y, 10 m | 4(Am) | c.[750G>A] (P) + c.[505C>T] (M) | Splice errors (P) + p. [Pro169Ser] (M) | 8 d | Salomons et al., 2007; novel |
| F12 | 16 y, 3 m | 11(Am) | c. [1429G>C] + c. [500A>G] | p. [Gly477Arg] + p. [Asn167Ser] | <24 h | Bennett et al., 2009 |
| F13 | 18 y, 10 m | 11(Am) | c. [1195G>C] + c. [749delT] | p. [Glu399Gln] + p. [Val250 frameshift] | 2 d | Mills et al., 2006; novel |
| F14 | 6 y, 10 m | 11(Am) | c. [1405+2T>C] + c. [1429G>C] | Splice errors + p. [Gly477Arg] | 4 d | Bennett et al., 2009; novel |
| F15 | 6 y, 9 m | 10(Lon) | c. [446C>A] + c. [446C>A] | p. [Ala149Glu] + p. [Ala149Glu] | 14 d | Novel |
| F16 | 3 y, 5 m | 8(Lon), 7(Lon) | c. [866C>T] +? | p. [Ser289Leu] +? | 5 d | Novel |
| F17 | 18 y, 8 m | 4(Am) | c.[1195G>C] (M) + c.[611+5G>A] | p. [Glu399Gln] (M) + Splice errors | 1 d | Mills et al., 2006; novel |
| F18 | 5 y, 6 m | 2.4(Lon) | c.[505C>T] (P) + c.[505C>T] (M) | p. [Pro169Ser] (P) + p. [Pro169Ser] (M) | 7 d | Novel |
| F19 | 17 y, 11 m | 1.3(Am) | c. [523T>G] (not P) +? | p. [Trp175Gly] +? | 14 m | Novel |
| F20 | 30 y, 4 m | n.m. | c. [244C>T] + c. [523T>G] | p. [Arg82Stop] + p. [Trp175Gly] | 8 m | Mills et al., 2006; novel |
| F21 | 3 y, 2 m | n.m. | c. [899A>G] (P) + c. [899A>G] (M) | Q300R (P) + Q300R (M) | 1 d | Novel |
| F22a | 15–26 y | n.m. | c. [385G>C] (P) + c. [1192A>C] (M) | A129P (P) + T398P (M) | 30 min | Novel; novel |
| F23 | 2 y | n.m. | c.[787+3del AAGT] + c.[787+3del AAGT] | p. [Gly263 frameshift] + p. [Gly263 frameshift] | <24 h | Novel |
| F24 | 22 y | n.m. | c. [157C>T] (P) + c. [157C>T] (M) | p. [R53Stop] (P) + p. [R53Stop] (M) | <4 d | Novel |
| F25 | 34 y, 9 m | n.m. | c. [750G>A] + c. [1195G>C] | Splice errors + p. [Glu399Gln] | Unknown | Mills et al., 2006; Salomons et al., 2007 |
| F26a | 17–20 y | n.m. | c.[434-1G>C] + c.[434-1G>C] | Splice errors + splice errors | <4 d | Mills et al., 2006 |
| F27b | 14–16 y | n.m. | c. [1140T>G] + c. [1140T>G] | p. [Y380Stop] + p. [Y380Stop] | <4 d | Mills et al., 2006 |
| F28 | 23 y, 9 m | n.m. | c.[1195G>C] (P) + c.[1195G>C] (M) | p. [Glu399Gln] (P) + p. [Glu399Gln] (M) | <4 d | Mills et al., 2006 |
| F29 | 5 y | n.m. | c.[890C>G] (M) + c.[1405+5G>A] (P) | p. [Thr297Arg] (M)+ Splice errors (P) | <7 d | Gallagher et al., 2009; Striano et al., 2009 |
| F30 | 22 y, 4 m | n.m. | c.419–422delTCTT + c.[1195G>C] | p. [Ile140 frameshift] + p. [Glu399Gln] | Unknown | Mills et al., 2006; Gallagher et al., 2009 |
Where parent DNA available inheritance was investigated and the allele carrying the mutation is indicated as: P (paternal) or M (maternal). n.m. = not measured; ? = no second mutation found; (Am) = sample analysed in Amsterdam (control range = <1 mmol/mol creatinine); (Lon) = sample analysed in London [Control range: <2.5 mmol/mol creatinine (<6 months), <1.5 mmol/mol creatinine (6–12 months), <1.0 mmol/mol creatinine (>12 months)]; y = years; m = months; d = days.
a Three affected siblings.
b Two affected siblings.