Table 2.
Individuals harboring the c.4723A>T mutation in CEP290.
| First Allele | Second Allele | |||||||
|---|---|---|---|---|---|---|---|---|
| Sample ID | Diagnosis | DNA Variant | Predicted Protein Variant | Predicted Proteins Based on RNA Study | DNA Variant | Predicted Protein Variant | Predicted Proteins Based on RNA Study | Ref. |
| Compound heterozygous | ||||||||
| Family A | OT | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] # | c.451C>T | p.(Arg151*) | p.[Arg151*, Leu148_Glu165del, Leu148_Lys172del] | This study |
| 809 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.1709C>G | p.(Ser570*) | ND | [10] |
| LCA-6 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.2991+1655A>G | p.(Cys998*) | p.[Cys998*, =] $ | [41] |
| LCA-7 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.2991+1655A>G | p.(Cys998*) | p.[Cys998*, =] | [41] |
| LCA-8 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.2991+1655A>G | p.(Cys998*) | p.[Cys998*, =] | [41] |
| LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.2991+1655A>G | p.(Cys998*) | p.[Cys998*, =] | [42] | |
| LCA-24 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4696G>C | p.(Ala1556Pro) | ND | [41] |
| COR031/CORS1 | CORS | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4393C>T | p.(Arg1465*) | ND | [10,43] |
| SLS-2 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4393C>T | p.(Arg1465*) | ND | [41] |
| SLS-3 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4393C>T | p.(Arg1465*) | ND | [41] |
| F283-21 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.1984C>T | p.(Gln662*) | ND | [44] |
| A3100-21 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.1987A>T | p.(Lys663*) | ND | [44] |
| A1210-21 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.3802C>T | p.(Gln1268*) | ND | [44] |
| F118-21 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4452_4455delAGAA | p.(Lys1484Asnfs*4) | ND | [44] |
| A1712-21 | SLSN | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.1189+1A>G | p.(?) | ND | [44] |
| Homozygous | ||||||||
| 1 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [46] |
| 2 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [46] |
| 738 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
| 848 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
| 258 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
| 419 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
| LEP | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
| LCA-25 | LCA | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [41] |
| 623 | JBTS+retina | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | c.4723A>T | p.(Lys1575*) | p.[Lys1575*, Glu1569_Trp1604del] | [10] |
Patient LCA-7 and LCA-25 are distantly related; LCA = Leber congenital amaurosis; SLSN = Senior loken; CORS = Cerebello-oculo-renal syndrome; JBTS+retina = Joubert syndrome with retinal involvement; # the mRNA carrying the p.(Lys1575*) mutation is the major product and the mRNA carrying the in-frame amino acid deletion p.(Glu1569_Trp1604del) is the minor product (see Figure 2); ND = not determined; $ = approximately equal amounts of mRNA were detected that contained an intronic insertion resulting in the p.(Cys998*) stop mutation and normal CEP290 transcript.