Supp. Table S3.
Clinical data of 80 patients with mutation(s) in one of the LCA genes Part I
| Gene | Patient n° | Gender | Night Blindness | Photophobia | ERG | Color vision | Fundus aspect | Other features |
|---|---|---|---|---|---|---|---|---|
| CEP290 p.[Cys998X]+[Cys998X] | LCA-1 | M | Absent (4mo) | Optic disc pallor Retinal vessel attenuation Normal macula | ||||
| CEP290 p.[Cys998X]+[Cys998X] | LCA-2 | M | Mild | Absent (5mo & 1.5yrs) | Pigmentary retinopathy Normal macula (6yrs) Retinal vessel attenuation Salt and pepper alterations Pseudopapilledema HyperAF ring around macula (14yrs) | Eyepoking | ||
| CEP290 p.[Cys998X]+[Arg108X] | LCA-3 | M | + | + | Absent (4mo) | + (6yrs) | Normal optic discs Retinal vessel attenuation Normal peripheral retina Beginning of hyperAF around macula (6yrs) | Eyepoking Enophthalmos |
| CEP290 p.[Cys998X(+ )Gln899X] | LCA-4 | F | Absent (2yrs) | Retinal vessel attenuation Tapetal reflex of posterior pole Pseudopapilledema | ||||
| CEP290 p.[Cys998X(+ )Arg1465X] | LCA-5 | M | Absent (4mo) | Eyepoking Enophthalmos | ||||
| CEP290 p.[Cys998X]+[Lys1575X] | LCA-6 | F | - | Strong (since 3.6yrs) | Severe CRD (3.3yrs) | B/Rand G/R | Retinal vessel attenuation White marbleized changes Macular oedema (3.2yrs) Retinal vessel attenuation White marbleized around vascular arcade Discrete RPE alterations No macular reflex (4.9yrs) Extensive peripheral outer retinal atrophy Limited spicular intraretinal pigmentation Relative macular preservation Relatively darker perifoveal ring (18yrs) | Exotropia |
| CEP290 p.[Cys998X(+ )Lys1575X] | LCA-7 | M | (+) (later in life) | + (early in life) | Subnormal (1yr) Absent (21yrs) | + (early in life) | Peripheral salt and pepper intraretinal pigmentation Relative macular preservation (22yrs) Extensive midperipheral and peripheral outer retinal atrophy Limited spicular intraretinal pigmentation Relative macular preservation Development of synchysis scintillans (33yrs) More extensive intraretinal pigmentation (predominantly spicular) Relative macular preservation Hyper AF in central macula and mid- and far periphery Extensive confluent atrophy (49yrs) | Eyepoking Enophthalmos Exotropia Posterior SCP cataract (star shaped) (49yrs) |
| CEP290 p.[Cys998X(+ )Lys1575X] | LCA-8 | F | Absent (16yrs) | R/G | Optic disc pallor | |||
| CEP290 p.[Cys998X]+[Arg1782X] | LCA-9 | M | + | Severe CRD (5mo & 1.2yrs) | Marbleized retinal changes | |||
| CEP290 p.[Cys998X]+[Asp128GlufsX17] | LCA-10 | F | Nummular pigmentation Pseudopapilledema Maculopathy | |||||
| CEP290 p.[Cys998X]+[Glu146GlyfsX17] | LCA-11 | M | Absent (6mo) | Optic disc pallor Yellow confluent peripheral spots | Eyepoking Enophthalmos | |||
| CEP290 p.[Cys998X(+)Arg621IlefsX2] | LCA-12 | M | Absent | Retinal vessel attenuation Peripheral pepper and salt alterations Macular RPE alterations (6mo) | Enophthalmos | |||
| CEP290 | LCA-13 | F | Absent | Optic disc pallor | ||||
| p.[Cys998X(+)Leu1141PhefsX5] | (4mo) | Retinal vessel attenuation | ||||||
| CEP290 p.[Cys998X]+[Thr1334IlefsX2] | LCA-14 | F | Absent (5mo) | Granular pigment alterations Normal macula (7mo) | Eyepoking Enophthalmos Cataract | |||
| CEP290 p.[Cys998X(+)Glu1656AsnfsX3] | LCA-15 (Perrault, Delphin et al. 2007) | M | - | Absent | Retinal vessel attenuation (7mo) Hyperaemic optic disc Marbleized, white spots Nummular pigmentation (2yrs) | Eyepoking Enophthalmos | ||
| CEP290 p.[Cys998X]+[Ala1832ProfsX19] | LCA-16 | M | Absent (6mo & 10mo) | Yellow spots | Eyepoking | |||
| CEP290 p.[Cys998X]+[Lys1840ArgfsX5] | LCA-17 | M | Absent (5mo) | Full optic disc with no apparent excavation Marbleized fundus changes in the midperiphery Normal macula (8yrs) | Eyepoking | |||
| CEP290 p.[Cys998X]+[Glu1956GlyfsX9] | LCA-18 | M | + (early in life) | Absent (3mo) | Full optic discs Limited outer retinal atrophy Midperipheral salt and pepper alterations Normal macula (15yrs) | Eyepoking Enophthalmos Keratoconus with acute hy drops (OD>OS)(13yrs) | ||
| CEP290 p.[Cys998X]+[Splice defect] | LCA-19 | M | + | + | Absent (3mo) | Very small optic disc excavation Retinal vessel attenuation Mild midperipheral salt and pepper alterations Bull's eye maculopathy with preservation of central macula, surrounded by concentric area of more pronounced outer retinal atrophy (14yrs) | Eyepoking Enophthalmos | |
| CEP290 p.[Cys998X(+)Splice defect] | LCA-20 (Yzer, Leroy et al. 2006) | F | - | - | Absent (9yrs) | Optic disc pallor Retinal vessel attenuation RPE alterations maculopathy unknown (3mo) | Eyepoking Enophthalmos Cataract with lens luxation Keratoconus (OD) Enucleation because of phacolytic glaucoma (OD) | |
| CEP290 p.[Cys998X]+[Splice defect] | LCA-21 | M | + | Absent | Optic disc pallor Retinal vessel attenuation | |||
| CEP290 p.[Cys998X(+)Splice defect] | LCA-22 | M | - | - | Absent (4mo & 9mo) | Normal optic discs White retinal spots Tapetal reflex | ||
| CEP290 p.[Cys998X(+)Splice defect] | LCA-23 | F | Absent (5mo& 1.5yrs) | Salt and pepper alterations Normal macula (5mo) Pinkish optic disc Mild retinal vessel attenuation RPE alterations (yellowish dots) (6yrs) | Eyepoking Enophthalmos | |||
| CEP290 p.[Lys1575X(+)Lys1575X] | LCA-24 | M | ||||||
| CEP290 p.[Lys1575X]+[Ala1566Pro] | LCA-25 | M | - | Strong | Severe CRD (1.1yrs) | No RPE alterations (4mo) Retinal vessel attenuation Discrete RPE alterations (1.10yrs) Retinal vessel attenuation HyperAF ring around macula (8yrs) Retinal vessel attenuation Salt and pepper alterations Mild macular pigment epithelial alterations (10yrs) | Eyepoking Enophthalmos Exotropia | |
| CEP290 p.[Leu1694Pr o]+[=, splice site] | LCA-26 | - | Absent (4.5yrs) | No retinal vessel attenuation No hyperpigmentation Midperipheral reticular aspect, especially around vascular arcades Assymetric ectopia foveae OS>OD (3yrs) Normal optic disc Deep intraretinal white spots along vascular arcades HyperAF ring around macula No pigmentation/atrophy (5.4yrs) | Strabismus | |||
| CEP290 p.Cys998X | LCA-27 | M | Subnormal (5mo & 1yr & 7yrs) | + | Optic disc pallor No RPE alterations Normal macula | |||
| CEP290 p.[Trp7Cys]+[ Trp7Cys] | SLS-1 | F | Absent (2mo) | Abnormal RPE | ||||
| CEP290 p.[Lys1575X( +)Arg1465X] | SLS-2 | F | + | + (12yrs) | Keratoconus Cataract | |||
| CEP290 p.[Lys1575X( +)Arg1465X] | SLS-3 | M | Eyepoking | |||||
| CEP290 p.[Lys1575X( +)Arg1465X] | CORS-1 (Brancati, Barrano et al. 2007) | F | Enophthalmos | |||||
| CEP290 p.[Gln1265X] +[Splice defect] | LCA-JS-1 | M | - | Absent (first year of life) | Optic disc pallor Salt and pepper alterations Mild spicular intraretinal pigmentation | |||
| CEP290 p.[Thr2457Al afsX27]+[Thr 2457AlafsX27] | LCA-JS-2II-1 | F | + | + | Absent | Normal optic discs Retinal vessel attenuation Salt and pepper alterations | ||
| LCA-JS-2II-1 | M | + | Absent | |||||
| CEP290 p.[Leu2448Th rfsX8(+)Splice defect] | LCA-JS-3 | M | + | Absent (4mo & 1.4yrs) | Optic disc pallor Retinal vessel attenuation | |||
| CRB1 p.[Lys801X(+)Lys801X] | LCA-28 | M | Marbleized fundus changes | |||||
| CRB1 p.[Lys801X(+)Gln362X] | LCA-29 (Yzer, Leroy et al. 2006) | M | + | Mild | Absent (1yr&30.6yrs) | Basic Severe R-G andB-Y deficienty | Optic disc pallor Retinal vessel attenuation Perivascular fibrosis No clear PPRPE Fine intraretinal white flecks Nummular intraretinal pigmentation Macular atrophy (30.6yrs) | Eyepoking (mild) Enophthalmos (mild) Posterior subcapsular cataract (OS>OD) |
| CRB1 p.[Lys801X]+[Arg764Cys] | LCA-30 | M | ||||||
| CRB1 p.[Lys801X]+[Cys896X] | LCA-31 (Yzer, Leroy et al. 2006) | M | + | - | Absent (3mo) | Basic | Retinal vessel attenuation Outer retinal atrophy RPE defects around vascular arcade Perimacular atrophic spots (3mo) Normal optic discs Perivascular fibrosis No clear PPRPE Outer retinal atrophy Small white dots Nummular hyperpigmentation Pseudopapilledema Macular atrophy (8yrs) | Eyepoking Enophthalmos Exotropia |
| CRB1 p.[Lys801X(+)Cys896X] | LCA-32 (Yzer, Leroy et al. 2006) | F | + | (+ after keratoconus) | Depigmentation around macula (15yrs) Macular aplasia: vessels of choroid become apparent (17yrs) Normal optic disc Retinal vessel attenuation Perivascular fibrosis No clear PPRPE Outer retinal atrophy White retinal spots Peripheral intraretinal pigment migration, predominant nummular Some midperipheral lipofuscin depositions Macular aplasia Pseudopapilledema (33yrs) | Eyepoking Enophthalmos Esotropia Keratoconus with acute hydrops and rupture of Descemet membrane (20yrs) | ||
| CRB1 p.[Lys801X(+)Cys948Tyr] | LCA-33 | F | + | Absent (9mo&1.7yrs) | Pale and slightly swollen optic disc Diffuse outer retinal atrophy Small whitish deep intraretinal flecks Nummular intraretinal pigmentation Limited macular atrophy | |||
| CRB1 p.[Lys801X]+[Splice defect] | LCA-34 | F | + | Absent (4mo & 1.5yrs) | Retinal vessel attenuation Macular pigmentation Pseudopapilledema | Eyepoking Strabismus | ||
| CRB1 p.[Cys948Tyr( +)Cys948Tyr] | LCA-35 | F | Keratoconus (OS) | |||||
| CRB1 p.[Cys948Tyr( +)Glu1330X] | LCA-36 | F | Optic disc pallor Retinal vessel attenuation Nummular intraretinal pigmentation Macular alterations Coats reaction | Enophthalmos Cataract Glaucoma (neovascular with OD seclusio pupillae and anterior synechiae) | ||||
| CRB1 p.[Cys948Tyr] +[Splice defect] | LCA-37 | M | + | |||||
| CRB1 p.[Cys948Tyr] +[Splice defect] | LCA-38 | M | + | - | Absent (9.1yrs) | Basic (until 9yrs) Disturbed (after 9yrs) | Optic disc pallor with irregular shape Retinal vessel attenuation Peripheral salt and pepper alterations (6yrs) Retinal vessel attenuation with tortuous aspect Extensive peripheral and macular outer retinal atrophy Small white deep intraretinal flecks Nummular intraretinal pigment migrations Yellowish hue of the macula 6 astrocytoma-like retinal excrescences superior to right macula Pseudopapilledema with prominent sheathing of blood vessels near optic discs (18yrs) | Eyepoking Enophthalmos Exotropia |
| CRB1 p.[Cys948Tyr] +[Splice defect] (LCA-39a) and p. [Splice defect]+[Splic e defect] (LCA-39b) | LCA-39a | F | + | + | Absent (4mo) | Basic (early in life) Declining at the age of 12yrs Absent (15.1 1yrs) | Optic disc pallor Retinal vessel attenuation Salt and pepper aspect Macular aplasia Total chorioretina atrophy in the central macula Pseudopapilledema Atrophic macular region with pigment near border (3yrs) Total atrophy of retina and choriocapillaris Midperipheral small white dots Midperipheral small nummular pigmentation | Eyepoking Enophthalmos Esotropia |
| LCA-39b | M | + | Absent (8yrs& 16yrs) | - | Optic disc pallor Small excavation optic disc (OD, not OS) Retinal vessel attenuation Extensive peripheral outer retinal atrophy Limited nummular intraretinal pigmentation Macular yellowish atrophy (OD>OS) (16yrs) | |||
| CRB1 p. [Splice defect(+)Splic e defect] | LCA-40 | M | + | - | Absent (2yrs) | No optic disc excavation No perivascular sheathing Severe outer retinal and central macular atrophy Small deep intraretinal white flecks Extensive nummular intraretinal pigmentation (11yrs) | Cataract (OS>OD) Retinal detachment (OD: partial -inferior, OS: total) | |
| CRB1 p.[Leu814Arg fsX23]+[Cys1 240ProfsX24] | LCA-41 II-1 | F | + | Mild | Absent (31yrs) | Disturbed | Hyperaemic optic disc Retinal vessel attenuation Small pigment clumps scattered through retina Pseudopapilledema Normal macula (12yrs) Macular atrophy with pigment clumping (21yrs) Macular pseudocoloboma (23yrs) Limited perivascular sheathing around optic disc Extensive outer retinal atrophy Small white intraretinal flecks Pronounced nummular intraretinal pigmentation Central macular atrophy (36yrs) | Eyepoking Enophthalmos Esotropia |
| LCA-41 II-2 | F | + | - | Absent (24yrs) | Disturbed | Beginning macular atrophy with pigment alterations (10yrs) Extensive peripheral outer retinal atrophy Extensive macular atrophy Extreme hyperpigmentation around central macula Pronounced peripapillary perivascular fibrosis Relative sparing of small retinal area just nasal to the optic disc (used for fixation) Pronounced mid and far-peripheral nummular intraretinal pigmentation (24yrs) | Eyepoking Enophthalmos Esotropia SCP Cataract (complete, OS) | |
| CRB1 p.[Trp1293X( +)Trp1293X] | LCA-42 | F | + | Absent (2yrs) | White retinal spots Salt and pepper pigmentation Maculopathy (2yrs) | Keratoconus Cataract (OD) | ||
| CRB1 p.[Cys948Tyr] +[Lys801X] | EORD-1 II-1 | F | + | - | CRD | Optic disc pallor Retinal vessel attenuation Salt and pepper alterations Nummular intraretinal pigmentation (over 360°) No maculopathy | ||
| EORD-1 II-2 | M | + | Mild | CRD | Optic disc pallor Salt and pepper alterations No maculopathy | |||
| CRB1 p.[Cys948Tyr(+)Cys310Tyr] | EORD-2 | M | Optic disc pallor Peripheral nummular intraretinal pigmentation No maculopathy | Cataract | ||||
| CRB1 p.[Cys948Tyr]+[Asp491Val] | EORD-3 | F | + (since the age of 5) | Strong (since early age) | Absent (4.10yrs) | Hyperaemic optic disc Retina vessel attenuation Midperipheral pigment alterations Pseudopapilledema Bull's maculopathy (4yrs) | ||
| CRB1 p.[Gln362X (+)Gln362X] | EORD-4 | M | Absent (5yrs) | Peripheral nummular intraretinal pigmentation No maculopathy | Cataract | |||
| CRB1 p.[Arg764Cys (+)Arg764Cys ] | EORD-5 | F | + (since the age of 13-14) | - | Absent (12yrs) | Normal (12yrs) | Pseudopapilledema Maculopathy (edema) Coats reaction (OD) Mid-peripheral spicular intraretinal pigmentation Excavation optic disc (OS) | SCP Cataract (OD) Glaucoma |
| RPE65 p.[Arg44Gln] +[Arg44Gln] | LCA-43 | F | Strong (since the age of 13-14) | (searches for light) | Absent (7mo & 2yrs) | R/B(not R/Y) (4yrs) | Discrete retinal vessel attenuation Normal fundus Very small white intraretinal flecks in mid- and far periphery No preretinal fibrosis (4yrs) | Esotropia |
| RPE65 p.[Pro181Leu]+[Pro181Leu] | LCA-44 | M | + | (searches for light) | Absent (5mo & 4yrs) | Disturbed | Retinal vessel attenuation Discrete RPE alterations (5mo) Optic disc pallor Retinal vessel attenuation Mild thinning of inferior retina Limited midperipheral intraretinal pigmentation Well-preserved macula (7yrs) | |
| RPE65 p.[Arg234X]+[Trp331dup] (LCA-45a) and p.[Trp331dup]+[Trp331dup] (LCA-45b) | LCA-45a LCA-45b | F | Optic disc pallor Depigmentations and round hyperpigmentations | |||||
| RPE65 p.Leu341Ser p.Ser121LeufsX6 (de novo) | LCA-46 | F | Retinal vessel attenuation Limited but clear peripheral outer retinal atrophy No intraretinal pigmentation Relative preservation of essentially normal macula (21yrs) | |||||
| RPE65 p.[Phe530Leu fsX40]+[Phe5 30LeufsX40] | LCA-47 | M | + | (searches for light) | Absent (9mo & 9yrs) | G/B R/0/P | Optic disc pallor Retinal vessel attenuation No pigmentation (5yrs) Normal optic discs Retinal vessel attenuation Discrete retinal thinning Cellophane maculopathy Limited macular pigment alterations Peripheral hypopigmentation Small discrete peripheral white flecks Total absence of AF (9yrs) | Eyepoking Cataract (very limited posterior lens opacification) Semimydriasis (ODS) |
| RPE65 p.[Phe530Leu fsX40]+[Arg1 24X] | LCA-48 | M | Absent (4mo & 1yr) | Basic | Optic disc pallor Retinal vessel attenuation Outer retinal atrophy especially in inferior midperiphery Relative sparing of the macula. Mild preretinal macular fibrosis | |||
| RPE65 p.[Phe530Leu fsX40]+[Splic e defect] | LCA-49 | M | Strong | (searches for light) | Absent (1.9yrs) | Basic | Retinal vessel attenuation No pigment alterations Normal macula (1yr&4.3yrs) Peripheral pigment alterations (6yrs) Normal optic disc Limited retinal vessel attenuation Peripheral RPE alterations without intraretinal pigment Very limited foveal pigment alterations | Semimydriasis |
| RPE65 p.[Arg296LysfsX7]+[Splice defect] | LCA-50 | F | Absent (5mo) | Normal vessels Mild RPE alterations No hyperpigmentation Normal macula | Esotropia Hypertropia | |||
| GUCY2D p.[Pro130Leuf sX36 (+)Splice defect] | LCA-51 | M | Absent (11mo&3yrs) | Normal fundus | Eyepoking | |||
| GUCY2D p.[Phe565Ser(+)Phe565Ser] | LCA-52 | M | Absent (6mo) | Normal fundus | Eyepoking Enophthalmos | |||
| GUCY2D p.[Arg768Trp(+)Arg768Trp] | LCA-53 | M | ||||||
| GUCY2D p.[Arg768Trp] +[Phe565Ser] | LCA-54 | F | + (since early age) | + (since the age of2.6) | Absent (3mo) | Normal fundus (1yr & 3.2yrs) | Eyepoking Enophthalmos Esotropia | |
| GUCY2D p.[Arg768Trp] +[Lys866Asn] | LCA-55 | M | Absent (4.4yrs) | - | Pseudopapilledema Essentially normal fundus Limited peripheral salt and pepper alterations Limited hyperAF of the central macula (13yrs) | Eyepoking | ||
| GUCY2D p.[Glu196Val]+[Pro711Leu] | LCA-56 | F | - | Strong | Absent (3mo) | Basic Strong R/G andB/Y defect | Optic disc pallor Retinal vessel attenuation Limited peripheral outer retinal atrophy No intraretinal pigmentation Normal macula Foveolar yellowish atrophy No hyper- or hypoAF (25yrs) | Eyepoking Enophthalmos Esotropia Keratoconus with acute hydrops (OD>OS) (16yrs) |
| GUCY2D p.Pro575Leu | LCA-57 | F | + | Absent (3.3yrs) | Severely disturbed | Optic disc hypoplasia Bull's maculopathy | ||
| AIPL1 p.[Trp278X]+[ Trp278X] | LCA-58 (Yzer, Leroy et al. 2006) | F | Mild | Absent (3mo & 1yr) | Bull's eye maculopathy, diffuse RPE alterations; limited intraretinal pigment migration of spicular type; sub- or deep intraretinal fine white deposits predominantly along vascular arcades | |||
| AIPL1 p.[Trp278X (+)Trp278X] | LCA-59 | M | + (since the age of4.10) | Absent (2yrs) | Retinal vessel attenuation No intraretinal pigmentation Macular pigment alterations (5yrs) | Eyepoking | ||
| AIPL1 p.[Trp278X (+)Trp278X] | LCA-60 | M | Normal optic discs Retinal vessel attenuation Peripheral outer retinal atrophy Spicular intraretinal pigmentation Total outer retinal aplasia of central macula, surrounded by thin rim of hyperplastic RPE (28yrs) | |||||
| AIPL1 p.[Trp278X]+[ Trp278X] | LCA-61 | F | + | Strong (after first decade) | Absent (3mo & 6mo) | Limited optic disc pallor Retinal vessel attenuation Extensive outer retinal atrophy Mid and far-peripheral spicular pigmentation Better preserved macula with central yellow atrophy (19yrs) | Eyepoking Esotropia | |
| AIPL1 p.[Thr114Ile; Pro376Ser] | LCA-62 | F | Absent (1.4yrs) | Optic disc pallor Retinal vessel attenuation | Eyepoking | |||
| CRX p.Tyr142Cys | LCA-63 | M | Absent (6mo) | Eyepoking | ||||
| CRX p.Val242Met | LCA-64 | M | ||||||
| RDH12 p.[Ala269Glyf sX2]+[Val233Asp] | EORD-6 | M | Optic disc pallor Retinal vessel attenuation Salt and pepper alterations | |||||
| RDH12 p.[Ala269Glyf sX2]+[Ser175Leu] | EORD-7 | M | + (since early age) | + | Absent (3.5yrs) | Basic (5.10yrs) | Limited retinal vessel attenuation Better preservation of the chorioretina in the posterior pole than in the periphery Clear retinal pigment epithelium alterations Peripheral areas of preserved chorioretina alternating with areas of total atrophy with predominant spicular intraretinal pigmentation (5yrs) Retinal vessel attenuation Yellowish discoloration of central macula More prominent spicular intraretinal pigmentation Areas with complete preservation of peripheral chorioretina (19yrs) | Esotropia |
| RDH12 p.[Ala269Glyf sX2(+)Ala269 GlyfsX2] | EORD-8 | |||||||
| RPGRIP1 p.Arg890X | LCA-65 | Strong | ||||||