Table 1.
Disease in 11 patients explained by mutations outside ABCA4
| ID / Cohort | Gene | NM# | Genotype | cDNA | Protein | Justification |
|---|---|---|---|---|---|---|
| 13 / Can | PRPH2 | NM_000322 | Heterozygous | c.37 C>T | p.(R13W) | Known (RP)34 |
| 55 / FC | CRB1 | NM_001193640 | Compound | c.635 G>A | p.(C212Y) | SIFT, PolyP |
| Heterozygous | c.2507 G>A | p.(C836Y) | Known AA (RP)35 | |||
| 57 / FC | PRPH2 | NM_000322 | Heterozygous | c.499 G>A | p.(G167S) | Known (PD) 26,36 |
| 61 / Can | DMD | NM_004010 | Homozygous | c.2458 C>T | p.(R820C) | SIFT, PolyP, H |
| 62 / Can | USH2A | NM_206933 | Compound | c.5953 G>A | p.(E1985K) | PolyP |
| Heterozygous | c.2802 T>G | p.(C934W ) | Known (RP) 37 | |||
| 69 / Can | BEST1 | M_004183 | Homozygous | c.830 C>T | p.(T277M) | SIFT, PolyP |
| 70 / Can | CDH23 | NM_001171930 | Homozygous | c.2263 C>T | p.(H755Y) | Known (USH1) 38-40 |
| 80 / FC | CRB1 | NM_001193640 | Compound | c.3350 G>C | p.(C1117S) | SIFT, PolyP |
| Heterozygous | c.493_501del | 165_167del | O | |||
| 96 / Can | CFH | NM_000186 | Homozygous | c.101 C>G | p.(T34R) | SIFT |
| 105 / FC | PROM1 | NM_006017 | Heterozygous | c.980 A>G | p.(N327S) | STGD |
| 145 / Chi | PROM1 | NM_006017 | Compound | c.2466 G>A | p.(M822I) | SIFT, STGD |
| Heterozygous | c.277-1 G>A | Splicing | Splice, STGD |
Patients who were clinically examined following the molecular diagnosis are in bold. Under Justification, “Known AA” indicates that the amino acid substitution is known to cause disease while “Known” indicates this specific DNA change is known to cause disease. The disease the mutation was associated with follows in parenthesis. RP stands for Retinitis Pigmentosa; PD stands for Pattern Dystrophy, USH1 stands for Usher Syndrome Type 1. FC = French Canadian, Can= other Canadian, Chi = Chinese. All novel mutations had a frequency <0.002 in a control cohort of 6,500 individuals (ESP6500). For novel mutations, use the following key: Sift = Predicted damaging by SIFT. PolyP = Predicted damaging by Polyphen 2. Splice = Predicted splice site loss mutation. STGD = This gene is known to cause Stargardt-like phenotypes. O=Overlaps with known disease causing missense and non-frameshift deletion mutations.