Table 1:
Properties of ABCA4 Variants and Age of Onset of STGD1 Patients
| Protein Variant (DNA Variant) | Relative Expression | Relative ATPase Activity ATPase–ATR +ATR | Function Index | Predicted Severity Class | Age of Onset Yr or decade [mean] | Reference |
|---|---|---|---|---|---|---|
| WT | 1.0 | 1.0 1.87±11 | 1.0 | Normal | ||
| p.Asn96Asp (c.286A>G) | 0.71±0.07 | 0.55±0.02 0.57±0.02 | 0.02 | Severe 1 | 23,14 8 [15] | (Salles et al., 2018) (Lambertus et al., 2015) |
| p.Asn96His (c.286A>C) | 0.61±0.17 | 0.23±0.08 0.19±0.08 | 0 | Severe 1 | 20 | (Simonelli et al., 2005) |
| p.Arg212Cys (c.634C>T) | 0.54±0.17 | 0.47±0.13 0.49±0.14 | 0.01 | Severe 1 | 11,11 8,10 [10] | (Fujinami et al., 2013) (Simonelli et al., 2000) |
| p.Arg602Trp (c.1804C>T) | 0.50±0.15 | 0.37±0.07 0.28±0.06 | 0 | Severe 1 | 8 15 [11.5] | (Ortube et al., 2014) (Riveiro-Alvarez et al., 2013)} |
| p.Asn965Ser (c.2894A>G) | 0.55±0.21 | 0.70±0.19 1.02±0.33 | 0.20 | Moderate 2 | 13,13,17,18 2nd decade [16] | (Rosenberg, Klie, Garred, & Schwartz, 2007) (Lee et al., 2017) (Riveiro-Alvarez et al., 2013) |
| p.Thr1019Met (c.3056C>T) | 0.17±0.06 | 0.26±0.04 0.31±0.06 | 0.01 | Severe 1 | 10, 10 [10] | (Fumagalli et al., 2001) |
| p.Glu1087Lys (c.3259G>A) | 0.54±12 | 0.37±0.23 0.31±0.18 | 0 | Severe 1 | <10 | (Fakin et al., 2016) |
| p.Arg1108Cys (c.3322C>T) | 0.28±0.05 | 0.40±0.03 0.75±0.21 | 0.11 | Moderate 2 | 10 | (Fakin et al., 2016) |
| p.Arg1129Leu (c.3386G>T) | 0.50±0.13 | 0.25±0.16 0.49±0.18 | 0.14 | Moderate 2 | 12,19,19, 31 20.6 [20.2] | (Valverde et al., 2006) (Riveiro-Alvarez et al., 2013) |
| p.Leu1430Pro (c.4289T>C) | 0.81±0.08 | 0.38±0.05 0.35±0.13 | 0 | Severe 1 | ~12 | (Rivera et al., 2000) |
| p.Gly1439Asp (c.4316G>A) | 0.74±0.16 | 0.41±0.03 0.46±0.11 | 0.04 | Severe 1 | 8 | (Lewis et al., 1999) |
| p.Pro1486Leu (c.4457C>T) | 0.84±0.16 | 0.56±0.06 0.87±0.33 | 0.30 | Moderate 2 | 25 | (Downes et al., 2012) |
| p.Ala1598Asp (c.4793C>A) | 0.64±0.19 | 0.48±0.21 0.32±0.12 | 0 | Severe 1 | 13 | (Burke et al., 2010) |
| p.Leu1940Pro (c.5819T>C) | 0.55±0.13 | 0.19±0.07 0.19±0.11 | 0 | Severe 1 | 6 | (Riveiro-Alvarez et al., 2013) |
| p.Gly1977Ser (c.5929G>A) | 0.73±0.07 | 0.13±0.08 0.15±0.02 | 0.02 | Severe 1 | 10 | (Riveiro-Alvarez et al., 2013) |
| p. Leu2027Phe (c.6079C>T) | 0.37±0.06 | 0.38±0.02 0.68±0.13 | 0.13 | Moderate 2 | 28 44 [36] | (Downes et al., 2012) (Fujinami et al., 2013) |
| p.Arg2030Gln (c.6089G>A) | 0.58±0.10 | 0.56±0.12 1.13±0.35 | 0.38 | Mild 3 | 52* | (Yatsenko, Shroyer, Lewis, & Lupski, 2001) (Fakin et al., 2016) |
| p.Arg2107His (c.6320G>A) | 0.90±0.17 | 0.66±0.13 1.23±0.17 | 0.59 | Mild 3 | 7th decade | (Zernant et al., 2014) |
| p.Cys2137Tyr (c.6410G>A) | 0.63±0.09 | 0.45±0.03 0.32±0.12 | 0 | Severe 1 | 7 | (Riveiro-Alvarez et al., 2013) |
| p.Gly863Ala (c.2588G>C) | 0.75±0.14 | 0.95±0.22 1.60±0.23 | 0.62 | Mild 3 | >50 not causal in homo-zygosity | (Westeneng-van Haaften et al., 2012) |
| p.Asn1868Ile (c.5603A>T) | 1.00±0.21 | 0.91±0.11 1.68±0.23 | 0.89 | Mild 3 | ND | |
| p.Gly863Ala/p.Asn1868Ile c.2588G>C/c.5603A>T | 0.73±0.13 | 0.80±0.15 1.50±0.27 | 0.59 | Mild 3 | ≥45 | (Zernant et al., 2017) |
Class 1 (Severe) F-index of 0 – 0.05; Class 2 (Moderate) F-index of 0.06 – 0.35; Class 3 (Mild) F-index > 0.35.
*
For a compound heterozygous patient with a null allele in trans. No homozygous patients reported. ND – No Data available