Table 2.
Disease-causing and likely pathogenic alleles (simple and complex) in ABCA4 (NM_000350.3) and their phenotypic effect in 24 Stargardt families from an isolated population.
| Family member | Variants identified | Age | Age dx | VA now | VF | CV defect | ERG | Phenotype |
|---|---|---|---|---|---|---|---|---|
| S1:III-4 | c.[5714 + 5G>A];[4163T>C] | 90 | 20 | R-CF L-CF | Central scotoma | Mild | NA | Central choroidal sclerosis |
| S1:III-6 | c.[5714 + 5G>A];[4163T>C] | 75 | 45 | R-CF 3 ft L-HM | Central scotoma | Medium | NA | STGD |
| S1:V-1 | c.4577C>T(;)4163T>C | NA | NA | NA | NA | NA | NA | NA |
| S2:IV-5 | c.[5714 +5G>A];[67-1delG] | 35 | 17 | R-20/400 L-20/400 | Central scotoma | Mild | Rod-normal cone-slight dec | CRD |
| S2:V-1 | c.[5714 + 5G>A];[67-1delG] | 16 | 14 | R-20/400 L-20/400 | Central scotoma | Mild | Rod-normal | CRD |
| S2:V-3 | c.[5714 + 5G>A];[67-1delG] | 20 | 18 | R-20/300 L-20/300 | Central scotoma | Mild | Rod-dec cone-normal | CRD |
| S3:II-1 | c.4469G>A(;)6089G>A(;)5603A>T | NA | NA | NA | NA | NA | NA | NA |
| S4:II-2 | c.[5714 + 5G>A];[5714 + 5G>A] | 56 | 52 | R-20/60 L-20/40 | Central scotoma | NA | Rod-slight dec cone-slight dec | STGD |
| S4:II-3 | c.[5714 + 5G>A];[5714 + 5G>A] | 66 | 47 | R-20/80 L-CF | Central scotoma | Severe | Rod-slight dec cone-slight dec | STGD |
| S5:II-2 | c.[4163T>C];[4163T>C] | NA | NA | NA | NA | NA | NA | NA |
| S5:II-4 | c.[4163T>C];[4163T>C] | NA | NA | NA | NA | NA | NA | NA |
| S5:III-1 | c.[5714 + 5G>A];[4163T>C] | 52 | 26 | R-20/400 L-20/300 | Central scotoma | Normal | Rod-dec cone-Normal | Atrophic macula |
| S6:III-1 | c.[5714 + 5G>A];[3322C>T] | 63 | 23 | R-CF L-CF | NA | Mild | Rod-normal cone-normal | STGD |
| S7:II-1 | c.[5714 + 5G>A];[5714 + 5G>A] | 56 | 26 | R-20/400 L-20/200 | Central scotoma | Mild | Rod-normal cone-normal | STGD |
| S8:II-2 | c.4577C>T(;)5603A>T | NA | NA | NA | NA | NA | NA | NA |
| S9:III-1 | c.[5714 + 5G>A];[5461-10T>C;5603A>T] | 67 | 12 | R-CF L-CF | Central scotoma correct | NA | Rod-dec cone-dec | CRD |
| S9:III-8 | c.[5714 + 5G>A;2588G>C];[5714 + 5G>A] | 46 | 29 | R-20/60 L-20/20 | Normal | Normal | Rod-normal cone-normal | STGD |
| S9:IV-1 | c.[5714 + 5G>A;2588G>C]; [5461-10T>C;5603A>T] | 21 | 15 | R-20/200 L-20/300 | Central scotoma | Medium | NA | STGD |
| S11:II-1 | c.[2588G>C;5603A>T];[6449G>A] | NA | NA | NA | NA | NA | NA | NA |
| S13:II-2 | c.[2588G>C;5603A>T];[4537delC] | NA | NA | NA | NA | NA | NA | NA |
| S16:II-4 | c.[2564G>A];[5461-10T>C;5603A>T] | 71 | 11 | R-HM L-HM | Peripheral islands only | Severe | NA | CRD |
| S16:IV-2 | c.[5461-10T>C;5603A>T]; [5461-10T>C;5603A>T] | 38 | 8 | R-20/400 L-20/400 | Peripheral Islands only | Severe | Rod-dec cone-dec | CRD |
| S16:IV-3 | c.[5461-10T>C;5603A>T]; [5461-10T>C;5603A>T] | 39 | 12 | R-20/400 L-CF | Mid-peripheral islands only | Severe | Rod-dec cone-dec | CRD |
| S16:IV-4 | c.[5714 + 5G>A];[5461-10T>C;5603A>T] | 41 | 13 | R-20/200 L-20/400 | Central scotoma | NA | Rod-dec cone-normal | CRD |
| S16:V-1 | c.[5461-10T>C;5603A>T]; [5461-10T>C;5603A>T] | 14 | 8 | R-20/500 L-20/300 | Central scotoma | Mild | Rod-dec cone-dec | CRD |
| S17:II-2 | c.[5714 + 5G>A];[5714 + 5G>A] | 62 | 39 | R-20/200 L-20/50 | Central scotoma | Severe | Rod-dec cone-normal | STGD |
| S17:II-3 | c.[5714 + 5G>A];[5714 + 5G>A] | 63 | 46 | R-20/30 L-CF | Central scotoma | NA | NA | STGD |
| S17:II-8 | c.[5714 + 5G>A];[5714 + 5G>A] | 52 | 41 | R-20/400 L-20/40 | Central scotoma | NA | Rod-slight dec cone-normal | STGD |
| S18:II-1 | c.2564G>A(;)4139C>T | NA | NA | NA | NA | NA | NA | NA |
| S19:II-3 | c.3322C>T(;)3323G>A | NA | NA | NA | NA | NA | NA | NA |
| S21:II-1 | c.[4139C>T];[4139C>T] | NA | NA | NA | NA | NA | NA | NA |
| S22:II-2 | c.[5714 + 5G>A];[2564G>A] | 57 | 14 | R-20/400 L-CF | Peripheral Islands | Severe | Rod-dec cone-dec | CRD |
| S23:II-3 | c.[5461-10T>C;5603A>T]; [5603A>T] | 52 | 14 | R-20/200 L-20/200 | NA | NA | NA | NA |
| S23-II-4 | c.[5461-10T>C;5603A>T]; [5603A>T] | 51 | 20 | R-CF L- 20/400 | NA | NA | NA | NA |
| S24:II-1 | c.[2564G>A;5603A>T] | NA | NA | NA | NA | NA | NA | NA |
| S24:II-3 | c.[2564G>A;5603A>T] | NA | NA | NA | NA | NA | NA | NA |
| S25:II-2a | c.4139C>T(;)5714 + 5G>A | 36 | 34 | R-20/20 L-20/25 | Small central scotomas | normal | NA | STGD |
| S26:II-1a | c.4577C>T(;)5714 + 5G>A | 32 | 12 | R-20/50−1 L-20/40−1 | Central scotoma | NA | Rod-slight dec cone-slight dec | NA |
| S27:II-2 | c.[5714 + 5G>A];[3322C>T] | 50 | NA | R-20/80 L-20/150 | Small central scotomas | NA | Rod-slight dec cone-normal | STGD |
| S28:II-1a | c.4163T>C(;)4469G>A | NA | NA | NA | NA | NA | NA | NA |
| S29:II-2a | c.5714 + 5G>A(;)634C>T | 47 | 45 | L-20/20 R-20/20 | Normal | NA | NA | STGD |
Bold indicates recurrent founder alleles.
CF counting fingers, HM hand motion, STGD Stargardt disease, CRD cone-rod dystrophy, NA not available, dec decreased, VA visual acuity, VF visual fields, dx diagnosis, ft feet, R right, L left, CV central vision, ERG electroretinogram.
aABCA4 genetic testing performed at Asper Biogene (no phasing information available).