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Supplementary information Supplementary information includes Figure S1, S2 and S3; Tables S1, S2, S3, S4 and S5. Figure S1. The genotype and phenotype of patient W29-1 A. Pedigree and mutations segregating within the family; B. Sequencing chromatograms of the family; C. ERG examination of the proband. Figure S2. The genotype and phenotype of patient W83-1 A. Pedigree and mutations segregating within the family; B. Sequencing chromatograms of the proband; C. Fundus image of the proband. Figure S3. The genotype and phenotype of patient W196-1 A. Pedigree and mutations segregating within the family; B. Sequencing chromatograms of the proband; C. The Y218C mutation is located in a highly conserved region; D. Fundus image of the proband. Table S1. List of 164 known retinal-disease genes. Gene Entrez Gene ID Chromosome Coding size (bp) ABCA4 24 1 6822 ABCC6 368 16 4512 ADAM9 8754 8 2460 AHI1 54806 6 3591 AIPL1 23746 17 1155 ALMS1 7840 2 12504 ARL6 84100 3 561 ATXN7 6314 3 2838 BBS1 582 11 1782 BBS10 79738 12 2172 BBS12 166379 4 2133 BBS2 583 16 2166 BBS4 585 15 1560 BBS5 129880 2 1026 BBS9 27241 7 2559 BEST1 7439 11 1815 C1QTNF5 114902 11 732 C2orf71 338939 2 3867 CA4 762 17 939 CABP4 57010 11 828 CACNA1F 778 X 5933 CACNA2D4 93589 12 3414 CC2D2A 57545 4 4863 CDH23 64072 10 3345 CDH3 1001 16 2490 CDHR1 92211 10 2580 CEP290 80184 12 7440 CERKL 375298 2 1545 CFH 3075 1 3696 CHM 1121 X 1962 CLN3 1201 16 1317 CLRN1 7401 3 738 CNGA1 1259 4 2280 CNGA3 1261 2 2085 CNGB1 1258 16 900 CNGB3 54714 8 2430 CNNM4 26504 2 2328 COL11A1 1301 1 5421 COL2A1 1280 12 4464 COL9A1 1297 6 2766 CRB1 23418 1 3885 CRX 1406 19 900 Exon No. 48 31 22 26 6 23 7 12 17 2 1 17 16 12 20 8 2 2 8 6 48 38 36 22 16 17 53 13 22 15 15 4 9 7 12 18 7 67 54 38 10 3 CYP4V2 DFNB31 DHDDS DMD EFEMP1 ELOVL4 EYS FAM161A FLVCR1 FSCN2 FZD4 GNAT1 GNAT2 GPR98 GRK1 GRM6 GUCA1A GUCA1B GUCY2D HMCN1 IDH3B IMPDH1 IMPG2 INPP5E INVS IQCB1 JAG1 KCNJ13 KCNV2 KLHL7 LCA5 LRAT LRP5 MAK MERTK MFRP MKKS MKS1 MTTP MYO7A NDP NPHP1 NPHP3 NPHP4 285440 285440 25861 79947 1756 2202 6785 346007 84140 28982 25794 8322 2779 2780 84059 6011 2916 2978 2979 3000 83872 3420 3614 50939 56623 27130 9657 182 3769 169522 55975 167691 9227 4041 4117 10461 83552 8195 54903 4547 4647 4693 4867 27031 261734 4 9 1 X 2 6 6 2 1 17 11 5 1 5 13 5 6 6 17 1 20 7 3 9 9 3 20 2 9 7 6 4 11 6 2 11 20 17 4 11 X 2 3 1578 2724 1002 11058 1482 945 9435 2151 1668 1479 1614 18921 1065 18921 2101 2634 606 603 3312 16908 702 1530 3726 1935 3198 1797 3657 285 1638 501 2094 693 4848 1872 3000 1740 1713 1680 2685 6648 402 2202 3993 11 12 8 79 10 6 40 7 10 5 2 90 8 90 7 10 4 4 18 107 6 14 15 10 16 13 26 2 2 5 7 2 23 13 19 13 4 18 18 48 2 20 27 1 4281 29 NR2E3 NRL NYX OAT OFD1 OPA1 OPA3 OPN1LW OPN1MW OPN1SW OTX2 PANK2 PAX2 PCDH15 PDE6A PDE6B PDE6C PDE6G PDZD7 PEX1 PEX7 PGK1 PHYH PITPNM3 PRCD PROM1 PRPF3 PRPF31 PRPF6 PRPF8 PRPH2 PXMP3 RAX2 RB1 RBP3 RBP4 RD3 RDH12 RDH5 RGR RGS9 RGS9BP RHO RIMS1 10002 4901 60506 4942 8481 4976 80207 5956 2652 611 5015 80025 5076 65217 5145 5158 5146 5148 79955 5189 5191 5230 5264 83394 768206 8842 9129 26121 24148 10594 5961 5828 84839 5925 5949 5950 343035 145226 5959 5995 8787 388531 6010 22999 15 14 X 10 X 3 19 X X 7 14 20 10 10 5 4 10 17 10 7 6 X 10 17 17 4 1 19 20 17 6 8 19 13 10 10 1 14 12 10 17 19 3 6 2102 741 1446 1320 3039 2883 543 1095 1095 1047 894 1713 1254 5874 2583 2562 2577 264 1554 3852 972 1254 1017 2925 165 2529 2052 1500 2826 7008 1041 918 555 2787 3744 606 588 951 957 762 2025 708 1047 5079 8 2 2 9 23 28 2 6 6 5 3 7 11 33 22 22 22 3 9 24 5 11 9 20 3 25 15 13 21 42 3 1 2 27 4 5 2 7 4 6 19 1 5 34 RLBP1 ROM1 RP1 RP1L1 RP2 RP9 RPE65 RPGR RPGRIP1 RPGRIP1L RS1 SAG SDCCAG8 SEMA4A SLC24A1 SNRNP200 SPATA7 TIMM8A TIMP3 TMEM126A TOPORS TRIM32 TRPM1 TSPAN12 TTC8 TTPA TULP1 UNC119 USH1C USH1G USH2A VCAN WFS1 ZNF513 Total 6017 6094 6101 94137 6102 6100 6121 6103 57096 23322 6247 6295 10806 64218 9187 23020 55812 1678 7078 84233 10210 22954 4308 23554 123016 7274 7287 9094 10083 124590 7399 1462 7466 130557 15 11 8 8 X 7 1 X 14 16 X 2 1 1 15 2 14 X 22 11 9 9 15 7 14 8 6 17 11 17 1 5 4 2 Table S2. List of 88 possible candidate genes. Gene Entrez Gene ID Chromosome ABLIM2 84448 4 ALDH1A2 8854 15 ANKRD33 341405 12 ARHGDIB 397 12 954 1056 6471 7203 1053 666 1602 3459 3861 3948 675 1218 2142 1890 3300 6411 1704 294 636 588 2943 1962 4812 918 1548 837 1629 723 2700 1386 15609 10191 2673 1440 460787 Coding size (bp) 1938 3606 1359 606 7 3 3 3 5 6 14 15 24 26 6 15 18 12 9 45 11 2 5 4 2 1 26 7 15 5 15 5 27 2 71 14 7 3 2654 Exon No. 21 13 5 5 ASCL1 ASH1L ATOH7 ATP6V1B2 BCAR1 BCL6 BTG2 CAMK1G CASZ1 CBLN4 CCKBR CCND1 CDK5R2 CHRNB4 CRB3 DACH1 EGFLAM EP300 ETV5 EYA1 EYA2 EYA3 EYA4 FBXW4 FOXF1 FOXG1 FOXM1 FOXN2 FOXN4 FOXO3 FOXP1 FOXP2 FOXS1 GABARAPL1 GLI3 HDAC4 HES1 IER5 IKZF1 KAT2A LHX2 MAB21L2 MEIS1 MITF 429 55870 220202 526 9564 604 7832 57172 54897 140689 887 595 8941 1143 92359 1602 133584 2033 2119 2138 2139 2140 2070 6468 2294 2290 2305 3344 121643 2309 27086 93986 2307 23710 2737 9759 3280 51278 10320 2648 9355 10586 4211 4286 12 1 10 8 16 3 1 1 1 20 11 11 2 15 19 13 5 22 3 8 20 1 6 10 16 14 12 2 12 6 3 7 20 12 7 2 3 1 7 17 9 4 2 3 711 8895 459 1536 2751 2121 477 1431 5280 606 1344 888 1104 1497 363 2127 3054 7245 1533 1779 1617 1722 1920 1239 1140 1470 2406 1296 1554 2022 2040 2223 993 354 4743 3255 843 984 1434 2514 1221 1080 1173 1563 1 27 1 14 7 8 2 11 18 3 5 5 1 6 4 11 23 31 12 16 15 17 19 9 2 1 7 5 9 2 16 17 1 4 14 26 4 1 6 18 5 1 12 10 NEUROD1 NEUROG2 NLK NR1D1 NR2E1 NR2F1 OTX1 PAX6 PIAS3 PITX3 POU2F2 PPARG PRDM1 RAC3 RARA RARB RARG RAX RCVRN RORB RXRA RXRB RXRG SIX1 SIX3 SIX6 SLC7A14 SMARCD3 SOX1 SOX2 SP1 SP4 TCF19 THRB TLL1 TREX1 TSHZ1 TSHZ2 TSHZ3 VSX2 Total 4760 63973 51701 9572 7101 7025 5013 5080 10401 5309 5452 5468 639 5881 5914 5915 5916 30062 5957 6096 6256 6257 6258 6495 6496 4990 57709 6604 6656 6657 6667 6671 6941 7068 7092 11277 10194 128553 57616 338917 2 4 17 17 6 5 2 11 1 10 19 3 6 17 17 3 12 18 17 9 9 6 1 14 2 14 3 7 13 3 12 7 6 3 4 3 18 20 19 14 1071 819 1584 1845 1158 1272 1065 1311 1887 909 1392 1518 2478 579 1389 1347 1365 1041 603 1380 1389 1614 1392 855 999 741 2316 1452 1176 954 2358 2355 1038 1386 3042 1110 3099 3105 3246 1086 154242 1 1 11 8 9 3 3 11 14 3 14 7 7 6 8 8 8 3 3 10 10 10 10 2 2 2 7 13 1 1 6 6 3 8 21 1 1 2 2 5 722 Table S3. List of 32 microRNAs. microRNAs Chromosome Location hsa-mir-9-1 1 207975197-207975284 hsa-mir-181b-1 1 220291499-220291583 hsa-mir-181a-1 11 568089-568198 hsa-mir-29c 11 64658827-64658911 hsa-mir-194-1 15 79502130-79502213 hsa-mir-210 15 89155056-89155165 hsa-mir-194-2 15 89911248-89911337 hsa-mir-184 19 13985513-13985622 hsa-mir-7-2 19 13985689-13985825 hsa-mir-9-3 19 4770682-4770791 hsa-mir-181c 2 56216085-56216194 hsa-mir-181d 2 56227849-56227930 hsa-mir-7-3 2 56210102-56210211 hsa-mir-216a 22 20020662-20020743 hsa-mir-216b 5 87962671-87962757 hsa-mir-217 6 33175612-33175721 hsa-mir-185 7 129414532-129414609 hsa-mir-9-2 7 129414745-129414854 hsa-mir-219-1 7 130135952-130136045 hsa-mir-96 7 99691183-99691266 hsa-mir-183 7 99691616-99691697 hsa-mir-335 7 129410223-129410332 hsa-mir-25 9 127454721-127454830 hsa-mir-106b 9 127455989-127456077 hsa-mir-182 9 131154897-131154993 hsa-mir-181a-2 9 21512114-21512184 hsa-mir-181b-2 9 73424891-73425000 hsa-mir-219-2 9 86584663-86584772 hsa-mir-31 X 85158641-85158712 hsa-mir-204 1 207975197-207975284 hsa-mir-7-1 1 220291499-220291583 hsa-mir-361 11 568089-568198 Table S4. Phenotypic and genotypic information in ninety-nine IRD patients. Patient ID Sex Age Diagnosis Onset age BCVA Family history Gene W5-1 W10-1 W33-1 W34-1 W37-1 M M M F F 34 36 31 30 29 RP RP RP RP RP 14 6 21 5 6 0.5/0.5 0.3/0.3 HM/HM FC/HM/ 0.4/0.4 AR XL S S* S EYS RPGR CRB1 CRB1 USH2A W132-1 W55-1 W115-1 W119-1 W127-1 W131-1 W146-1 W155-1 W156-1 W159-1 W171-1 W172-1 W177-1 W214-1 W286-1 W106-1 W139-1 F67-1 F5-1 F7-1 F9-1 F10-1 F11-1 F12-1 F23-1 F25-1 F29-1 F31-1 F33-1 F35-1 F39-1 H2-1 H3-1 H4-1 H12-1 S4-1 S7-1 S11-1 W76-1 W83-1 W84-1 W136-1 W59-1 W67-1 M F F M F F M F M M F F F M M M F F F M M M M M F M M M M M M M F F F M M F M F M F M F 12 40 20 40 48 60 32 39 27 34 37 38 48 49 43 23 32 26 36 34 22 23 48 67 25 48 26 20 21 43 54 59 34 43 57 23 50 38 47 67 32 42 43 37 RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP 5 20 10 20 20 20 5 30 15 20 20 27 10 35 20 5 15 5 26 15 6 5 41 20 20 10 6 10 15 13 40 41 20 39 43 5 10 5 20 10 20 32 20 10 0.16/0.2 0.25/0.5 0.12/0.12 HM/HM 0.2/0.04 LP/NLP 0.6/0.6 0.1/0.06 0.3/0.1 0.5/0.4 FC/FC 0.1/0.4 LP/LP FC/FC FC/0.05 HM/HM 0.4/0.5 FC/FC 0.8/0.8 HM/0.01 0.08/0.09 0.25/0.2 0.4/0.4 0.07/0.08 0.12/0.1 0.12/0.15 0.5/0.5 0.8/0.8 0.2/0.2 0.2/0.2 HM/FC LP/LP 1/1.2 0.08/0.08 0.06/0.06 0.4/0.5 LP/0.1 0.04/0.01 0.1/0.3 FC/FC 0.5/0.3 0.8/0.7 0.3/0.4 0.8/0.6 XL S S S* AR AR* S* S S AR* S* AR AR S* S S* AR* AR AD AR XL AR S S S XL S S S S AR AD S S AR S S S S S S AD S S RP2 SNRNP200 RPE65 RP1 EYS USH2A CNGA1 CYP4V2 CERKL EYS EYS CYP4V2 RP1 CNGB1 EYS RP1 PDE6A MERTK RHO USH2A RP2 RLBP1 EYS PRPF31 ABCA4 RPGR USH2A RLBP1 PROM1 EYS CERKL PRPF31 MAK PRPF31 USH2A PITPNM3 PDE6B RHO CYP4V2 RHO PDE6B TOPORS SNRNP200 PDE6B W69-1 W82-1 W86-1 W89-1 W90-1 W92-1 W93-1 W13-1 W50-1 W74-1 W75-1 W78-1 W99-1 W44-1 W181-1 W32-1 W11-1 W31-1 W124-1 W130-1 W133-1 W176-1 W272-1 W197-1 H9-1 W56-1 W1-1 W141-1 W290-1 W138-1 W169-1 W105-1 W152-1 W154-1 F14-1 W72-1 W58-1 W96-1 W111-1 W205-1 W140-1 W142-1 W149-1 W9-1 M F M M F M F M M F M M M F F M M M M M M M M F F M M F F M M F M M F M M M F M M M M M 35 43 25 35 44 41 10 63 30 62 31 31 60 49 18 22 24 28 26 41 36 45 52 30 47 41 8 4 3 7 2 4 31 10 22 37 42 56 27 48 14 43 34 40 RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP RP Usher Usher Usher Usher Usher Usher Usher Usher Usher Usher LCA LCA LCA LCA LCA LCA CRD CRD CRD CRD CRD CRD Stargardt Stargardt Stargardt Stargardt Stargardt BCD 20 22 15 32 30 21 5 41 25 22 20 20 20 5 5 15 14 16 5 5 5 30 10 20 33 5 4 1 1 5 1 1 20 6 10 20 20 10 10 18 10 30 5 30 HM/HM 0.5/0.5 0.6/0.6 0.2/0.2 0.4/0.15 0.1/0.08 FC/0.3 0.15/0.2 LP/LP 0.25/0.25 0.2/0.2 0.3/0.4 LP/LP 0.04/0.04 0.12/0.1 0.5/0.6 0.3/0.3 0.4/0.6 0.15/0.4 HM/HM FC/FC 0.5/0.4 FC/0.6 0.4/0.25 0.08/0.08 HM/HM FC/FC ND ND 0.4/0.5 ND LP/LP 0.12/0.1 0.3/0.25 0.1/0.1 FC/FC 0.3/LP FC/FC 0.06/0.08 LP/LP 0.16/0.16 0.16/0.1 0.05/0.05 0.04/0.04 S* S S S AD AD S AR AR AD S* S* AR AD S S AR S S S* S* AR* AR S AR S S S S S S S S* S S AR* S S S AR S AD S S CYP4V2 EYS EYS RPGR RHO PROM1 CRB1 EYS CYP4V2 PRPF6 EYS MERTK USH2A PRPF6 USH2A USH2A USH1C USH2A USH2A USH2A USH2A USH2A USH2A USH2A CLRN1 USH2A CRB1 CRB1 CRB1 RPE65 CEP290 AIPL1 CDHR1 CACNA1F CRX KCNV2 CACNA2D4 CACNA1F ABCA4 PROM1 ABCA4 PROM1 ABCA4 CYP4V2 W15-1 W20-1 W129-1 F8-1 W196-1 W29-1 M M M F F F 41 48 10 44 35 9 BCD BCD CSNB CSNB RP ESCS 21 25 5 5 10 5 HM/HM 0.07/HM 0.2/0.3 0.2/0.15 LP/LP 0.4/0.8 AR* AR S AD S S* CYP4V2 CYP4V2 PDE6B PDE6B AHI1 NR2E3 M, male; F, female; RP, retinitis pigmentosa; Usher, Usher Syndrome; LCA, Leber congenital amaurosis; CRD, cone-rod dystrophy; BCD, Bietti crystalline dystrophy; CSNB, congenital stationary night blindness; ESCS, enhanced S cone syndrome; BCVA, best corrected visual acuity; HM, hand movement; FC, fingers count, LP, light perception; NLP, no light perception; AR, autosomal recessive; AD, autosomal dominant; XL, X-linked; S, simplex; asterisk indicates the consanguineous families. Table S5. Mutations identified in ninety-nine IRD patients. Patient Gene Mutation Type a Seg b W10-1 W33-1 RPGR CRB1 W34-1 W37-1 CRB1 USH2A W132-1 W55-1 W115-1 RP2 SNRNP200 RPE65 c.2006G>A, p.W669X c.2480G>A, p.G827E c.137delA c.3676G>T, p.G1226X c.7068T>G, p.N2356K c.5752G>A, p.E1918K c.884-1G>C c.1614T>G, p.I538M c.311G>A, p.G104D c.272G>A, p.R91Q c.380G>A, p.W127X c.6557G>A, p.G2186E c.9186_9187delCA c.6908C>T, p.S2303F c.15562A>G, p.S5188G c.1271G>A, p.R424Q c.1091-2A>G c.810delT c.451T>G, p.W151G c.758delT c.7492G>C, p.A2498P c.7609G>A, p.A2537T c.7949C>T, p.S2650F c.1091-2A>G c.810delT c.3223G>T, p.E1075X c.254_255insC c.1631C>T, p.P544L c.6416G>A, p.C2139Y c.8150delA Hemi Hetero Hetero Homo Hetero Hetero Hemi Hetero Hetero Hetero Homo Hetero Hetero Hetero Hetero Homo Hetero Hetero Hetero Hetero Homo Hetero Hetero Hetero Hetero Hetero Hetero Homo Hetero Hetero Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes W119-1 W127-1 RP1 EYS W131-1 USH2A W146-1 W155-1 CNGA1 CYP4V2 W156-1 CERKL W159-1 W171-1 EYS EYS W172-1 CYP4V2 W177-1 RP1 W214-1 W286-1 CNGB1 EYS Prediction c PolyPhen-2 SIFT ND ND Damaging Tolerated ND ND ND ND Damaging Tolerated Damaging Tolerated ND ND Damaging Damaging Damaging Damaging Damaging Tolerated ND ND Damaging Damaging ND ND Damaging Damaging Damaging Tolerated Damaging Tolerated ND ND ND ND Damaging Damaging ND ND Damaging Damaging Damaging Damaging Damaging Damaging ND ND ND ND ND ND ND ND Damaging Tolerated Damaging Damaging ND ND Frequency d Hapmap 1K None None None None None None None None Rare Rare None None None None None None None Rare None Rare None None None None None None None None Rare Rare Rare Rare Rare Rare Rare Rare None None None None None None Rare Rare None None Rare Rare Rare Rare None None None None Rare Rare Rare Rare None None Reference Novel Novel Novel 1 2 Novel 3 Novel Novel 4 Novel 5 Novel Novel 6 7 8 Novel Novel 9 Novel Novel Novel 8 Novel Novel Novel Novel 5 Novel W106-1 W139-1 F67-1 F5-1 F7-1 RP1 PDE6A MERTK RHO USH2A F9-1 F10-1 F11-1 RP2 RLBP1 EYS F12-1 F23-1 PRPF31 ABCA4 F25-1 F29-1 RPGR USH2A F31-1 F33-1 F35-1 RLBP1 PROM1 EYS F39-1 CERKL H2-1 H3-1 H4-1 H12-1 PRPF31 MAK PRPF31 USH2A S4-1 S7-1 PITPNM3 PDE6B S11-1 W76-1 RHO CYP4V2 W83-1 RHO c.678delA c.357delT c.1691-1G>A c.1030C>T, p.Q344X c.13010C>T ,p.T4337M c.8559-2A>G c.358C>T, p.R120X c.282delC c.2510G>T, p.C837F c.8107G>T, p.E2703X c.910C>T, p.R304C c.1531C>T, p.R511C c.6479+1G>C c.935-2A>G c.13010C>T, p.T4337M c.11389+1G>C c.282delC c.1824delT c.8012T>A, p.L2671X c.704G>A, p.W235X c.547A>T, p.I183F c.1404delA c.629delC c.552G>C, p.W184C c.1305T>A, p.Y435X c.15017C>T, p.T5006M c.4307C>T, p.P1436L c.2233G>A, p.G745R c.1669C>T, p.H557Y c.167_171del5bp c.403C>T, p.R135W c.694C>T, p.R232X c.810delT c.628G>T, p.V210F Homo Homo Homo Hetero Hetero Hetero Hemi Homo Hetero Hetero Hetero Hetero Hetero Hemi Hetero Hetero Homo Homo Hetero Hetero Hetero Hetero Hetero Homo Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes ND ND ND ND Damaging ND ND ND Damaging ND Damaging Damaging ND ND Damaging ND ND ND ND ND Damaging ND ND Damaging ND Damaging Damaging Damaging Damaging ND Damaging ND ND Damaging ND ND ND ND Damaging ND ND ND Damaging ND Damaging Damaging ND ND Damaging ND ND ND ND ND Damaging ND ND Damaging ND Tolerated Damaging Damaging Damaging ND Damaging ND ND Damaging None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None Rare None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None Rare None Novel Novel Novel 10 11 12 13 Novel Novel Novel Novel 14 14 Novel 11 Novel Novel Novel Novel Novel Novel 15 Novel Novel Novel Novel Novel Novel 7 Novel 7 16 Novel 17 W84-1 W136-1 W59-1 W67-1 PDE6B TOPORS SNRNP200 PDE6B W69-1 CYP4V2 W82-1 EYS W86-1 EYS W89-1 W90-1 W92-1 W93-1 RPGR RHO PROM1 CRB1 W13-1 EYS W29-1 W50-1 NR2E3 CYP4V2 W74-1 W75-1 W78-1 W99-1 PRPF6 EYS MERTK USH2A W44-1 W181-1 PRPF6 USH2A W32-1 USH2A W11-1 USH1C W31-1 USH2A c.1133G>A, p.W378X c.2598_2609del11bp c.1631T>C, p.M544T c.1219G>A, p.G407R c.1712C>T, p.T571M c.958C>T, p.R320X c.810delT c.7492G>C, p.A2498P c.8244_8245insT c.6416G>A, p.C2139Y c.8392delG c.2377C>T, p.Q793X c.403C>T, p.R135W c.1117C>T, p.R373C c.1831T>C, p.S611P c.1576C>T, p.R526X c.3489T>A, p.N1163K c.2644T>C, p.F882L c.290G>A, p.R97H c.1027T>G, p.Y343D c.694C>T, p.R232X c.514C>T, p.R172W c.6416G>A, p.C2139Y c.1690+1G>A c.9469C>T, p.Q3157X c.2802T>G, p.C934W c.551A>G, p.D184G c.15562A>G, p.S5188G c.2617G>A, p.G873R c.9259G>A, p.V3087I c.100_101insT c.463C>T, p.R155X c.311G>A, p.G104D c.5581G>A, p.G1861S Homo Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hemi Hetero Hetero Hetero Hetero Hetero Hetero Homo Hetero Hetero Hetero Homo Homo Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes ND ND Damaging Damaging Tolerated ND ND Damaging ND Damaging ND ND Damaging Damaging Damaging ND Damaging Tolerated Damaging Damaging ND Damaging Damaging ND ND Damaging Damaging Damaging Damaging Tolerated ND ND Damaging Damaging ND ND Damaging Damaging Damaging ND ND Tolerated ND Damaging ND ND Damaging Damaging Damaging ND Tolerated Damaging Damaging Damaging ND Damaging Damaging ND ND Damaging Damaging Tolerated Tolerated Tolerated ND ND Damaging Damaging None None None Rare None None Rare None None Rare None None None None None None Rare Rare None None None None Rare None None Rare None Rare None Rare None None None None None None None Rare None None Rare None None Rare None None None Rare None None Rare Rare None None None None Rare None None Rare None Rare None Rare None None None None Novel Novel Novel Novel Novel 18 Novel Novel Novel 5 Novel Novel 7 19 1 1 20 Novel 21 Novel 16 Novel 5 Novel 22 23 Novel 6 Novel Novel Novel 24 25 22 W124-1 USH2A W130-1 W133-1 W176-1 W272-1 USH2A USH2A USH2A USH2A W197-1 USH2A H9-1 CLRN1 W56-1 USH2A W1-1 CRB1 W141-1 CRB1 W290-1 CRB1 W138-1 RPE65 W169-1 CEP290 W105-1 W152-1 W154-1 F14-1 W72-1 W58-1 W96-1 W111-1 AIPL1 CDHR1 CACNA1F CRX KCNV2 CACNA2D4 CACNA1F ABCA4 W205-1 PROM1 c.4576G>A, p.G1526R c.5581G>A, p.G1861S c.15427C>T, p.R5143C c.9469C>T, p.Q3157X c.4576G>A, p.G1526R c.8559-2A>G c.8559-2A>G c.8917_8918delCT c.9801C>G, p.C3267W c.802G>A, p.G268R c.149C>A, p.S50X c.253+6T>C c.2209C>T, p.R737X c.8603delA c.455G>A, p.C152Y c.1985C>A, p.S662X c.1841G>T, p.G614V c.3442T>C, p.C1148R c.1148G>A, p.C383Y c.2498G>A, p.G833D c.917C>T, p.T306I c.912C>A, p.Y304X c.451C>T, p.R151X c.4195-1G>C c.421C>T, p.Q141X c.1117C>T, p.Q373X c.2932C>T, p.R978X c.790G>A, p.V264M c.1284_1287delTGTC c.2120G>A, p.R707H c.1464G>T, p.E488D c.5584G>C, p.G1862R c.1804C>T, p.R602W c.436C>T, p.R146X Hetero Hetero Hetero Homo Homo Homo Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Hetero Homo Homo Hemi Hetero Homo Homo Hemi Hetero Hetero Hetero Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Damaging Damaging Tolerated ND Damaging ND ND ND Damaging Damaging ND ND ND ND Damaging ND Damaging Damaging Damaging Damaging Damaging ND ND ND ND ND ND Damaging ND Damaging Damaging Damaging Damaging ND Tolerated Damaging Damaging ND Tolerated ND ND ND Damaging Damaging ND ND ND ND Damaging ND Damaging Damaging Damaging Damaging Damaging ND ND ND ND ND ND Damaging ND Tolerated Tolerated Damaging Damaging ND None None Rare None None None None None None None None None None None None None None None Rare None None None None None None None None None None None None None None None None None Rare None None None None None None None None None None None None None None None Rare None None None None None None None None None None None None None None None Novel 22 22 22 Novel 12 12 Novel Novel 26 Novel Novel 23 22 27 Novel 28 Novel Novel 29 Novel Novel 30 Novel Novel Novel Novel Novel Novel Novel Novel Novel 14 Novel c.1229_1230delCT Hetero Yes ND ND None None Novel 31 c.2894A>G, p.N965S Homo Yes Damaging Damaging None Rare 19 c.1117C>T, p.R373C Hetero Yes Damaging Damaging None Rare 31 c.2894A>G, p.N965S Hetero Yes Damaging Damaging None Rare c.6479+4A>G Hetero Yes ND ND None None Novel 8 W9-1 CYP4V2 c.992A>C, p.H331P Hetero Yes Damaging Damaging None None 8 c.1091-2A>G Hetero Yes ND ND Rare Rare 8 W15-1 CYP4V2 c.1091-2A>G Homo Yes ND ND Rare Rare 8 W20-1 CYP4V2 c.992A>C, p.H331P Homo Yes Damaging Damaging None None W129-1 PDE6B c.1624C>T, p.R542W Hetero Yes Damaging Damaging None None Novel 7 F8-1 PDE6B c.1811C>T, p.T604I Hetero Yes Damaging Damaging None None W5-1 EYS c.9368A>C, p.N3123T Hetero Yes Tolerated Damaging None None Novel 5 c.6416G>A, p.C2139Y Hetero Yes Damaging Damaging Rare Rare W196-1 AHI1 c.653A>G, p.Y218C Hetero Yes Damaging Damaging None None Novel 32 c.3257A>G, p.E1086G Hetero Yes Damaging Damaging Rare Rare a Mutation type: Hetero, heterozygous; Homo, homozygous; Hemi, hemizygous. b Seg, co-segregation. c Prediction of functional effects of missense mutations by using PolyPhen-2 and SIFT. ND, nonsense, frameshift or splice site mutations are not detected. d Allele frequencies: none, absent in the database; rare, less than 0.01. W140-1 W142-1 W149-1 ABCA4 PROM1 ABCA4 References 1. Li L, Xiao XS, Li SQ, et al. Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis. PLoS One. 2011;6. 2. Glockle N, Kohl S, Mohr J, et al. Panel-based next generation sequencing as a reliable and efficient technique to detect mutations in unselected patients with retinal dystrophies. Eur J Hum Genet. 2013. 3. Neidhardt J, Glaus E, Lorenz B, et al. Identification of novel mutations in X-linked retinitis pigmentosa families and implications for diagnostic testing. Mol Vis. 2008;14:1081-1093. 4. Morimura H, Fishman GA, Grover SA, Fulton AB, Berson EL, Dryja TP. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis. Proc Natl Acad Sci U S A. 1998;95:3088-3093. 5. 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