Table 1.
Gene mutations in 121 unrelated Caucasian patients with presenting diagnosis of OCA
| Gene | Patient | Age | Clinical diagnosis | Molecular diagnosis | Consanguinity | Mutation 1 | Mutation 2 | Other |
|---|---|---|---|---|---|---|---|---|
| TYR | 1 | 4 | OCA1A | OCA1A | − | c.1118C>A (T373K) | c.1164delT | |
| 2 | 21 | OCA1A | OCA1A | − | c.1147G>A (D383N) | c.1467insT | ||
| 3 | Adult | OCA1A | OCA1A | − | c.1118C>A (T373K) | c.338-339delCA | ||
| 4 | 27 | OCA1A | OCA1A | − | c.232G>T (E78X) | c.1336G>A (G446S) | ||
| 5 | 17 | OCA1A | OCA1A | − | c.1118C>A (T373K) | c.1146C>A (N382K) | ||
| 6 | 2m | OCA1A | OCA1A | − | c.649C>G (R217G) | c.1204C>T (R402X) | ||
| 7 | Child | OCA1A | OCA1A | − | c.61C>T (P21S) | c.1164delT | ||
| 8 | Adult | OCA1A | OCA1A | − | c.242C>T (P81L) | c.649C>G (R217G) | ||
| 9 | Child | OCA1A | OCA1A | − | c.1118C>A (T373K) | c.1336G>A (G446S) | ||
| 10 | 4 | OCA1A | OCA1A | − | c.542A>G (Y181C) | c.1118C>A (T373K) | TYR: S192Y (H); SLC45A2: L374F (h) | |
| 11 | Adult | OCA1A | OCA1A | − | c.238T>C (W80R) | c.1336G>A (G446S) | TYR: R402Q (H) | |
| 12 | 30 | OCA1A | OCA1A | − | c.1118C>A (T373K) | c.1184G>A (S395N) | ||
| 13 | 8 | OCA1A | OCA1A | − | c.140G>A (G47D) | c.242C>T (P81L) | ||
| 14 | Adult | OCA1A | OCA1A | + | c.242C>T (P81L) | c.242C>T (P81L) | ||
| 15 | Adult | OCA1A | OCA1A | − | c.25delC | c.1336G>A (G446S) | ||
| 16 | Adult | OCA1A | OCA1A | − | c.1118C>A (T373K) | c.1147G>A (D383N) | ||
| 17 | Child | OCA1A | OCA1A | − | c.1118C>A (T373K) | c.1336G>A (G446S) | ||
| 18 | 6m | OCA1A | OCA1A | − | c.164G>A (C55Y) | c.242C>T (P81L) | TYR: S192Y (H); SLC45A2: L374F (h) | |
| 19 | 5 | OCA1A | OCA1A | − | c.446A>G (Y149C) | c.1132C>T (Q378X) | ||
| 20 | 45 | OCA1A | OCA1A | − | c.446A>G (Y149C) | c.1118C>A (T373K) | ||
| 21 | 6m | OCA1A | OCA1A | − | c.1118C>A (T373K) | c.1336G>A (G446S) | ||
| 22 | 9 | OCA1A | OCA1A | − | c.25delC | c.650G>A (R217Q) | ||
| 23 | 47 | OCA1A | OCA1A | − | c.242C>T (P81L) | c.649C>T (R217W) | ||
| 24 | Adult | OCA1A | OCA1A | + | c.242C>T (P81L) | c.242C>T (P81L) | ||
| 25 | Child | OCA1A | OCA1A | + | c.242C>T (P81L) | c.242C>T (P81L) | ||
| 26 | Adult | OCA1A | OCA1A | − | c.619G>A (A206T) | c.1204C>T (R402X) | ||
| 27 | 29 | OCA1A | OCA1A | − | c.1118C>A (T373K) | c.572delG | TYR: S192Y (H), R402Q (H); SLC45A2: L374F (h) | |
| 28 | 37 | OCA1A, mental retardation | OCA1A | ? | c.1147G>A (D383N) | c.1147G>A (D383N) | Karyotype normal | |
| 29 | 5m | OCA | OCA1A | − | c.1118C>A (T373K) | c.1204C>T (R402X) | ||
| 30 | 10m | OCA | OCA1A | − | c.1118C>A (T373K) | c.1075C>T (Q359X) | TYR: R402Q (H) | |
| 31 | 9 | OCA | OCA1A | − | c.286-287insA | c.896G>A (R299H) | ||
| 32 | Adult | OCA | OCA1A | − | c.613C>A (P205T) | c.896G>A (R299H) | SLC45A2: L374F (h) | |
| 33 | 8m | OCA1B | OCA1A | − | c.346C>T (R116X) | c.649delC | ||
| 34 | 9 | OCA1B | OCA1A | − | c.650G>A (R217Q) | c.1336G>A (G446S) | ||
| 35 | 4 | OCA1A | OCA1B | − | c.823G>T (V275F) | c.1118C>A (T373K) | ||
| 36 | 2m | OCA1A | OCA1B | − | c.1217C>T (P406L) | c.1255G>A (G419R) | TYR: S192Y (H); SLC45A2: L374F (h) | |
| 37 | Child | OCA1A | OCA1B | − | c.140G>A (G47D) | c.1037-7T>A (IVS2-7T>A) | ||
| 38 | 3 | OCA1A | OCA1B | − | c.823G>T (V275F) | c.1118C>A (T373K) | ||
| 39 | 7 | OCA1A | OCA1B | − | c.823G>T (V275F) | c.731-732delGT | ||
| 40 | 68 | OCA1A | OCA1B | − | c.1118C>A (T373K) | c.1265G>A (R422Q) | ||
| 41 | 69 | OCA1A | OCA1B | − | c.605A>G (H202R) | c.1342G>A (D448N) | ||
| 42 | 3m | OCA1A | OCA1B | − | c.1037-7T>A (IVS2-7T>A) | c.1118C>A (T373K) | ||
| 43 | 24 | OCA1A | OCA1B | − | c.299C>T (R77W) | c.823G>T (V275F) | ||
| 44 | Adult | OCA1A | OCA1B | − | c.1265G>A (R422Q) | — | TYR: R402Q (h); SLC45A2: L374F (h) | |
| 45 | 6m | OCA1B? | OCA1B | − | c.823G>T (V275F) | c.1037-7T>A (IVS2-7T>A) | ||
| 46 | 5 | OCA1B? | OCA1B | − | c.1209G>T (R403S) | c.1342G>A (D448N) | ||
| 47 | 4 | OCA1B? | OCA1B | − | c.895C>A (R299S) | c.1118C>A (T373K) | OCA2: R419Q (H) | |
| 48 | 11m | OCA1B | OCA1A | − | c.650G>A (R217Q) | c.1467insT | SLC45A2: L374F (H) | |
| 49 | 41 | OCA1B | OCA1B | − | c.1265G>A (R422Q) | c.1336G>A (G446S) | ||
| 50 | 36 | OCA1B | OCA1B | − | c.61C>T (P21S) | c.1342G>A (D448N) | ||
| 51 | Adult | OCA1B | OCA1B | − | c.823G>T (V275F) | c.242C>T (P81L) | ||
| 52 | 4 | OCA1B | OCA1B | − | c.1037-7T>A (IVS2-7T>A) | c.880G>A (E294K) | ||
| 53 | 7 | OCA1B | OCA1B | − | c.1037-7T>A (IVS2-7T>A) | c.1037-7T>A (IVS2-7T>A) | ||
| 54 | 6m | OCA1B | OCA1B | − | c.242C>T (P81L) | c.823G>T (V275F) | ||
| 55 | 18m | OCA1B | OCA1B | − | c.1037-7T>A (IVS2-7T>A) | c.1168C>G (H390D) | ||
| 56 | 26 | OCA1B | OCA1B | − | c.242C>T (P81L) | c.823G>T (V275F) | ||
| 57 | 82 | OCA1B | OCA1B | − | c.1063G>C (A355P) | c.1342G>A (D448N) | ||
| 58 | 23 | OCA1B | OCA1B | − | c.1037-7T>A (IVS2-7T>A) | c.1138T>C (S380P) | ||
| 59 | 15m | OCA1B | OCA1B | − | c.1A>G (M1V) | c.1217C>T (P406L) | TYR: S192Y (H); SLC45A2: L374F (h) | |
| 60 | 17m | OCA1B | OCA1B | − | c.650G>A (R217Q) | c.823G>T (V275F) | TYR: R402Q (H); SLC45A2: L374F (h) | |
| 61 | 2 | OCA1B | OCA1B | − | c.650G>A (R217Q) | c.823G>T (V275F) | TYR: S192Y (H), R402Q (H) | |
| 62 | 20 | OCA1B | OCA1B | − | c.823G>T (V275F) | c.1501insC | ||
| 63 | 8 | OCA1B | OCA1B | − | c.1037-7T>A (IVS2-7T>A) | Total deletion of TYR | ||
| 64 | Adult | OCA1B | OCA1B | − | c.242C>T (P81L) | c.1265G>A (R422Q) | TYR: R402Q (H) | |
| 65 | 37 | OCA1B | OCA1B | + | c.1217C>T (P406L) | c.1217C>T (P406L) | ||
| 66 | 70 | OCA1B | OCA1B | − | c.1265G>A (R422Q) | c.649C>T (R217W) | ||
| 67 | 19 | OCA1B | OCA1B | − | c.1265G>A (R422Q) | c.124delG | ||
| 68 | 10m | OCA1B | OCA1B | − | c.650G>A (R217Q) | c.864A>T (L288F) | TYR: R402Q (h); SLC45A2: L374F (h) | |
| 69 | 8m | OCA1B | OCA1B | − | c.1037-7T>A (IVS2-7T>A) | c.1037-7T>A (IVS2-7T>A) | SLC45A2: L374F (h) | |
| 70 | 10 | OCA1B | OCA1B | − | c.1217C>T (P406L) | c.1217C>T (P406L) | TYR: c.1063G>C (A355P), c.1291C>A (P431T) | |
| 71 | 14m | OCA1B | OCA1B | − | c.823G>T (V275F) | — | ||
| 72 | 10 | OCA1B | OCA1B | − | c.1366+4A>G (IVS4+4A>G) | — | TYR: S192Y (H) | |
| 73 | 4 | OCA1B, mental retardation | OCA1B | − | c.973A>G (T325A) | — | TYR: R402Q (H); karyotype normal | |
| 74 | 3m | OCA1A | OCA1 | − | c.344-345delGA | c.368T>C (I123T) | ||
| 75 | Child | OCA1A | OCA1 | − | c.140G>A (G47D) | — | OCA2: R305W (h) | |
| 76 | 12m | OCA1A | OCA1 | − | c.1118C>A (T373K) | — | TYR: S192Y (H) | |
| 77 | 14m | OCA1A | OCA1 | − | c.731-732delGT | — | ||
| 78 | 6m | OCA1A | OCA1 | − | c.1118C>A (T373K) | — | TYR: R402Q (H), S192Y (h); OCA2: IVS5-19A>G (H); SLC45A2: L374F (H) | |
| 79 | 10 | OCA1A | OCA1 | − | c.1118C>A (T373K) | — | TYR: R402Q (H) | |
| 80 | Child | OCA1A | OCA1 | − | c.1164delT | — | TYR: S192Y (H) | |
| 81 | 12m | OCA1B | OCA1 | − | c.1118C>A (T373K) | — | TYR: R402Q (H), S192Y (h); SLC45A2: L374F (h) | |
| 82 | 9m | OCA1B, mental retardation | OCA1 | − | c.250T>G (F84V) | — | TYR: R402Q (H), S192Y (h); SLC45A2: L374F (h); karyotype normal | |
| 83 | 28m | OCA1B, mental retardation | OCA1 | − | c.1336G>A (G446S) | — | ||
| 84 | ? | OCA | OCA1 | − | c.626C>T (P209L) | c.1118C>A (T373K) | TYR: S192Y (H); SLC45A2: L374F (h) | |
| OCA2 | 85 | 7 | OCA2, PWS | OCA2 | − | c.1327G>A (V443I) | Deletion 15q11.2-q13.1 | |
| 86 | 10 | OCA2, Angelman syndrome | OCA2 | − | c.1327G>A (V443I) | Deletion 15q11.2-q13 | ||
| 87 | 8m | OCA1B/OCA2 | OCA2 | − | c.1327G>A (V443I) | c.1465A>G (N489D) | ||
| 88 | 12m | OCA1B/OCA2 | OCA2 | − | c.79G>A (G27R) | c.79G>A (G27R) | TYR: R402Q (H); OCA2: L440F (h); HPS4: E229G (H), V552 M (h), H606Y (h), Q625H (h) | |
| 89 | 4m | OCA1B/OCA2 | OCA2 | − | c.1327G>A (V443I) | c.2228C>T (P743L) | TYR: R402Q (H); TYRP1: R93H (H) | |
| 90 | 4 | OCA2 | OCA2 | − | c.1327G>A (V443I) | c.2228C>T (P743L) | ||
| 91 | 28 | OCA2 | OCA2 | − | c.79G>A (G27R) | c.2207C>T (S736L) | OCA2: L440F (H) | |
| 92 | 18 | OCA2 | OCA2 | − | c.1327G>A (V443I) | c.1327G>A (V443I) | ||
| 93 | 6 | OCA2 | OCA2 | − | c.1441G>A (A481T) | c.1465A>G (N489D) | OCA2: R305W (H) | |
| 94 | 22 | OCA2 | OCA2 | − | c.79G>A (G27R) | c.79G>A (G27R) | SLC45A2: L374F (h); HPS4: E229G (h), L443V (H), V552 M (h), H606Y(h), Q625H (h) | |
| 95 | 12m | OCA2 | OCA2 | − | c.1327G>A (V443I) | c.1327G>A (V443I) | TYR: R402Q (H); SLC45A2: L374F (h) | |
| 96 | 5m | OCA2 | OCA2 | − | c.79G>A (G27R) | c.79G>A (G27R) | OCA2: L440F (h); HPS4: E229G (h), V552 M (h), H606Y (h), Q625H (h) | |
| 97 | 8 | OCA2 | OCA2/AROA | − | c.1441G>A (A481T) | c.1842+1G>T (IVS17+1G>T) | ||
| 98 | 3 | OCA2 | OCA2 | − | c.482delG | — | OCA2: R305W (H) | |
| 99 | 5 | OCA2 | OCA2 | − | c.1327G>A (V443I) | — | TYR: R402Q (H); OCA2: R266W (H); HPS4: E229G (H), V552 M (H), H606Y (H), Q625H (H) | |
| 100 | 11m | OCA2/multiple congenital anomalies | OCA2 | − | c.1327G>A (V443I) | — | TYR: R402Q (H); SLC45A2: L374F (h); HPS4: E229G (h), V552 M (h), H606Y (h), Q625H (h) | |
| 101 | 7m | OCA1B/OCA2 | OCA2 | − | c.1327G>A (V443I) | — | TYR: S192Y (H), R402Q (H); OCA2: R419Q (H); SLC45A2: L374F (h); HPS4: E229G (h), L443V (H), V552 M (h), H606Y (h), Q625H (h) | |
| 102 | 7m | OCA1B/OCA2 | OCA2 | − | c.79G>A (G27R) | — | TYR: S192Y (H); OCA2: R305W (H), L440F (H); SLC45A2: L374F (H); HPS4: H235R (H), E229G (h), V552 M (h), H606Y (h), Q625H (h) | |
| 103 | 3 | OCA1B/OCA2 | OCA2 | − | c.1951+1G>A (IVS18+1G>A) | — | TYR: S192Y (h); SLC45A2: L374F (H) | |
| 104 | 4 | OCA1A/1B | OCA2 | − | c.1465A>G (N489D) | — | OCA2: R305W (h) | |
| 105 | 15 | OCA1B | OCA2 | − | c.1901T>A (I634N) | — | ||
| 106 | ? | OCA | OCA2 | − | c.79G>A (G27R) | — | TYR: S192Y (H), R402Q (H); OCA2: L440F (H); SLC45A2: L374F (h) | |
| SLC45A2 | 107 | 3m | OCA1A | OCA4 | − | c.298G>A (G100S) | — | TYR: R402Q (h); OCA2: IVS5-19A>G (H); SLC45A2: H94D (H), L374F (h) |
| 108 | Adult | OCA1A | OCA4 | − | c.1164-1166delAA | — | TYRP1: A24T (H) | |
| 109 | 11 | OCA1B | OCA4 | − | c.301C>T (R101C) | c.1074-1077delAG | TYR: P152S (H) | |
| 110 | 75 | OCA2 | OCA4 | − | c.130G>A (G44R) | c.1004T>G (M335R) | ||
| 111 | 23 | OCA2 | OCA4 | − | c.593G>A (G198D) | c.1502C>A (A501D) | TYR: S192Y (h); SLC45A2: L374F (h) | |
| 112 | 10 | OCA2 | OCA4 | − | c.834C>G (Y278X) | — | SLC45A2: S143R (H) | |
| 113 | 7 | OCA | OCA4 | ? | c.986delC | c.986delC | TYR: S192Y (H) | |
| No mutations | 114 | 13m | OCA1A | — | − | — | — | HPS4: E229G (H), L443V (H), V552 M (H), H606Y (H), Q625H (H) |
| 115 | 3 | OCA2 | — | ? | — | — | TYR: S192Y (H); SLC45A2: L374F (h) | |
| 116 | 10 | OCA2 | — | ? | — | — | HPS4: E229G (h), L443V (H), V552 M (h), H606Y (h), Q625H (h) | |
| 117 | Child | OCA2 | — | − | — | — | SLC45A2: L374F (h); HPS4: E229G (h), V552 M (h), H606Y (h), Q625H (h) | |
| 118 | 4m | OCA | — | ? | — | — | OCA2: IVS21+18A>G (H); SLC45A2: L374F (h); HPS4: E229G (h), V552 M (h), H606Y (h), Q625H (h) | |
| 119 | 31 | OCA | — | − | — | — | OCA2: R419Q (H); HPS1: P491R (H), Q603R (H); HPS4: E229G (h), L443V (H), V552 M (h), H606Y (h), Q625H (h) | |
| 120 | Adult | OCA | — | ? | — | — | TYR: S192Y (H), R402Q (H); OCA2: R305W (H); HPS4: E229G (h), L443V (H), V552 M (h), H606Y (h), Q625H (h) | |
| 121 | Child | OCA | — | ? | — | — | HPS4: E229G, V552 M, H606Y, Q625H (h) |
(H), heterozygous; (h), homozygous
All subjects were subjected to DNA sequence analysis of the TYR (OCA1), OCA2, TYRP1 (OCA3), SLC45A2 (OCA4), HPS1, HPS4, and SILV genes. Overall, 84 (69%) patients had OCA1, 22(18%) OCA2, 0 OCA3, and 7 (6%) OCA4; 8 (7%) had no identifiable gene mutations and so could not be classified.