Table 2.
Identified potential pathogenic variants in Leber congenital amaurosis (LCA)- and other inherited retinal dystrophies (IRD)-associated genes.
| Disorder | Gene | Accession number | Variant type | Nucleotide change | Location in gene | Patients found to harbour variant | SNP ID | Database listingsa | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| HGVD | ToMMo | 1000 Genomes | ExAC | ||||||||
| LCA | CRB1 | NM_201253.2 | Insertion | c.668dupT;p.(L223Ffs*4) | Exon 3 | EYE68 | 0 | 0 | 0 | 0 | |
| c.733dupG;p.(A245Gfs*16) | Exon 3 | EYE68 | 0 | 0 | 0 | 0 | |||||
| c.1567dupC;p.(L523Pfs*28) | Exon 6 | EYE68 | 0 | 0 | 0 | 0 | |||||
| Nonsense | c.1576C > T;p.(R526*) | Exon 6 | EYE115 | rs114342808 | 0 | 0.0002 | 0 | 4.94 × 10−5 | |||
| Deletion | c.1334_1740del;p.(C445Yfs*8) | Exon 6 | EYE115 | 0 | 0 | 0 | 0 | ||||
| Missense | c.2T > C;p.? | Exon 1 | EYE121 | 0 | 0 | 0 | 0 | ||||
| c.3068T > G;p.(L1023R) | Exon 9 | EYE121 | 0 | 0.0002 | 0 | 0 | |||||
| NMNAT1 | NM_022787.3 | Missense | c.1A > G;p.? | Exon 2 | EYE42 | 0 | 0 | 0 | 8.26 × 10−6 | ||
| c.196C > T;p.(R66W) | Exon 3 | EYE159, S132 | 0 | 0.0002 | 0 | 0.0001 | |||||
| c.709C > T;p.(R237C) | Exon 5 | EYE42, EYE159, S132 | rs375110174 | 0.0009 | 0.0002 | 0 | 7.42 × 10−5 | ||||
| RPGRIP1 | NM_020366.3 | Deletion | c.3565_3571delCGAAGGC;p.(R1189Gfs*7) | Exon 22 | EYE20, EYE64, EYE65, EYE170 | 0 | 0 | 0 | 1.66 × 10−5 | ||
| Splicing | c.1467 + 1G > T | Intron 11 | EYE55 | 0 | 0 | 0 | 0 | ||||
| Deletion | Exon 17 deletion (c.2710 + 374_2895 + 74del) | Exon 17 | EYE55, EYE16, JU0954, JU0955 | 0 | 0 | 0 | 0 | ||||
| Nonsense | c.799C > T;p.(R267*) | Exon 5 | EYE149 | rs554396590 | 0 | 0 | 0.0002 | 8.36 × 10−6 | |||
| c.1687C > T;p.(R563*) | Exon 13 | EYE149 | 0 | 0 | 0 | 0 | |||||
| GUCY2D | NM_000180.3 | Splicing | c.2113 + 2_2113 + 3insT | Intron 10 | LCA1H (Twin 1 and 2) | 0 | 0 | 0 | 0 | ||
| Missense | c.2714T > C;p.(L905P) | Exon 14 | LCA1H (Twin 1 and 2) | 0 | 0 | 0 | 0 | ||||
| c.2765A > G;p.(Y922C) | Exon 14 | EYE139 | 0 | 0.0003 | 0 | 0 | |||||
| c.2983C > T;p.(R995W) | Exon 16 | EYE139 | rs61750187 | 0 | 0 | 0 | 0 | ||||
| CEP290 | NM_025114.3 | Deletion | c.2390delA;p.(K797Sfs*2) | Exon 23 | EYE69 | rs781670422 | 0 | 0 | 0 | 5.10 × 10−5 | |
| Nonsense | c.6889A > T;p.(K2297*) | Exon 50 | EYE69 | 0 | 0 | 0 | 0 | ||||
| CRX | NM_000554.4 | Missense | c.124G > A;p.(E42K) | Exon 3 | EYE70 | rs863224863 | 0 | 0 | 0 | 0 | |
| IMPDH1 | NM_000883.3 | Missense | c.590A > C;p.(Q197P) | Exon 8 | EYE125 | 0 | 0 | 0 | 0 | ||
| LRAT | NM_004744.4 | Missense | c.163C > T;p.(R55W) | Exon 2 | JU1039, JU1040 | rs527236079 | 0.0018 | 0.0025 | 0 | 0 | |
| Deletion | Exon 1–3 deletion | Exon 1–3 | JU1039, JU1040 | 0 | 0 | 0 | 0 | ||||
| PRPH2 | NM_000322.4 | Deletion/ Insertion | c.730_736delinsCAGCTCCTCCAGACGGGTGCACCAGAC;p.(N244Qfs*19) | Exon 2 | EYE156 | 0 | 0 | 0 | 0 | ||
| Missense | c.748T > G;p.(C250G) | Exon 2 | EYE156 | 0 | 0 | 0 | 0 | ||||
| Other IRD | RP2 b | NM_006915.2 | Splicing | c.769-2A > G | Intron 2 | EYE114 | 0 | 0 | 0 | 0 | |
| RPGR b | NM_000328.2 | Missense | c.977A > C;p.(K326T) | Exon 9 | EYE50 | 0 | 0 | 0 | 0 | ||
| BEST1 c | NM_004183.3 | Missense | c.682G > T;p.(D228Y) | Exon 6 | EYE187 | 0 | 0 | 0 | 0 | ||
aDatabases include: 1000 Genomes database (1000 Genomes; http://www.1000genomes.org/), Exome Aggregation Consortium database (ExAC; http://exac.broadinstitute.org/), Human Genetic Variation Database (HGVD; http://www.genome.med.kyoto-u.ac.jp/SnpDB/), and Tohoku Medical Megabank Organization database (ToMMo; https://ijgvd.megabank.tohoku.ac.jp/).
bRPGR and RP2 mutations have been previously shown to cause X-linked retinitis pigmentosa (RP).
cMutations in BEST1 gene have been shown to cause Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, adult-onset vitelliform macular dystrophy, autosomal dominant vitreoretinochoroidopathy, and autosomal dominant RP.
AD, autosomal dominant; AR, autosomal recessive; XL, X-linked.