(a–c) Fundus images depicting the spectrum of retinal findings in p.Arg245* USH1F patients, show mottling of pigment epithelium, attenuation of retinal vasculature, and pallor of optic nerve head …
(a–c) Left eye fundus autofluorescence in (c) shows a central area, delineated by white arrowheads, of complete loss of autofluorescence consistent with RPE atrophy (compare with normal fundus …
(a) Quantification of scotopic (dark adapted) responses from littermate control (Pcdh15+/+ or Pcdh15R250X/+) and mutant (Pcdh15R250X/R250X) mice at 1 month of age revealed progressive loss of both …
(a) Confocal micrographs of P97 mouse retinae from control and Pcdh15R250X mutants immunostained for protocadherin-15 (PCDH15, cyan, left panel) and opsin to label outer segments (OS, magenta, center…
(a) Average thresholds of acoustic brainstem response (ABR) to broadband clicks and tone-pips with frequencies of 8 kHz, 16 kHz, and 32 kHz in control (Pcdh15R250X/+; black) and mutant (Pcdh15R250X/R…
Confocal micrographs of P60 organ of Corti (a) and vestibular end organs (b) of control (Pcdh15R250X/+) and mutant (Pcdh15R250X/R250X) mice immunostained with myosin VIIa antibody (green) and …
(a) Representative ERG waveforms from 1-month-old mice of the denoted genotypes show normal wave architecture with significantly reduced waveforms for mutant mice. (b) b/a ratio shows the mutant …
(a) Representative confocal micrographs of light-adapted retinae show mislocalization of phototransduction cascade proteins, arrestin, and transducin, to both the inner segment (IS) and outer …
(a) Representative confocal micrographs of dark-adapted retinae show the correct localization of phototransduction cascade proteins, transducin to the outer segment (OS), and arrestin to the inner …
Transmission electron micrographs of 1–2-month-old mice of denoted genotype show normal RPE with no obvious structural abnormalities, irrespective of genotype. Scale bar: 2 µm. Data presented as …
(a, d) Representative scotopic ERG traces from young (2–3 months) (a) and old (6–7 months) (d). 9-cis retinal injected Pcdh15 mutant mice (right panels) show waveforms comparable to vehicle-injected …
(a) Eye and (b) liver. Student’s unpaired t-test, p<0.05 (*), ns. not significant.
(a) Representative confocal micrographs of light-adapted retinae from vehicle-injected control mice (Pcdh15R250X/+), exhibit the correct localization of phototransduction cascade proteins, …
Eleven patients in this study are homozygous for the p.Arg245* variants while two siblings carry compound heterozygous variants, ¥p.Arg245*/p.Arg929*. Visual acuity assessments consistently show a …
Age (years) | BCVA OD; OS | Visual field OD | Visual field OS | Lens | Macula | Spicules/mottling | Optic nerve | |
---|---|---|---|---|---|---|---|---|
LMG210 #1563 | 12 | 20/25; 20/30 | 90, ND, ND | 90, ND, ND | Clear | Normal | N/A | N/A |
22 | 20/40; 20/50 | 30, 0, 0 | 28, 0, 0 | Mild PSC | Pigment | Spicules | Pale | |
35 | HM; HM | 20, 0, 0 | 15, 0, 0 | PSC | Atrophy | Spicules | Pale +3 | |
LMG279 #1795 | 19 | 20/25; 20/32 | 50, 15, 0 | 65, 18, 0 | PSC | Normal | Spicules | Pale |
LMG268 #1722 | 37 | 20/30; 20/30 | 23, 14, 10 | 20, 12, 10 | PSC | Normal | Spicules | Pale |
50 | 20/160; 20/50 | 12, 1, 0 | 15, 2, 0 | PSC | Atrophy OD | Spicules | Pale | |
59 | LP; 20/500 | 0, 0, 0 | 6, 0, 0 | PSC+NS | Atrophy | Spicules | Pale | |
67 | LP; HM | ND | ND | PSC+NS OD; | Atrophy | Spicules | Pale | |
IOL OS | ||||||||
LMG178 #1463 | 25 | 20/100; 20/30 | ND | ND | Mild PSC | CME | Spicules | ONH swelling |
26 | 20/50; 20/40 | 30, 8, 0 | 35, 25, 0 | Mild PSC | CME | Spicules | Resolved swelling | |
LMG200 #1539 | 8 | 20/30; 20/30 | ND | ND | N/A | N/A | N/A | N/A |
25 | 20/50; 20/40 | 40, 0, 0 | 40, 0, 0 | Clear | Atrophy | Spicules | Pale+1 | |
LMG200 #1538 | 6 | 20/40; 20/30 | ND | ND | N/A | N/A | N/A | N/A |
22 | 20/100; 20/60 | 6, 0, 0 | 9, 0, 0 | Clear | Atrophy | Spicules | Pale+1 | |
LMG186 #1484 | 21 | 20/30; 20/40 | HVF | HVF | Mild PSC | Normal | Spicules | Pale |
Diameter 5° | Diameter 10° | |||||||
LMG407 #2149 | 55 | 20/400; 20/300 | 3, 0, 0 | 5, 0, 0 | IOL OU | Atrophy | Spicules | Pale +3 |
LMG322 #1917 | 22 | 20/60; 20/30 | 140, 30, 0 | 145, 30, 0 | Clear | CME | Spicules | Normal |
LMG322 #1916 | 11 | 20/25; 20/25 | 110, 35, 0 | 110, 30, 0 | Clear | Normal | Spicules | Normal |
16 | 20/25; 20/25 | 110, 35, 0 | 110, 30, 0 | Clear | Normal | Spicules | Normal | |
LMG125 #1221 | 12 | 20/30; 20/30 | ND | ND | Clear | CME, ERM | Spicules | Pale |
LMG197 #1831¥ | 30 | 20/50, 20/50 | 80, 7, 0 | 100, 10, 0 | PSC | Normal | Spicules | Pale +1 |
38 | 20/60, 20/60 | 40, 0, 0 | 60, 4, 0 | PSC | Atrophy | Spicules | Pale +2 | |
50 | 20/160, 20/100 | 15, 0, 0 | 22, 0, 0 | PSC | Atrophy | Spicules | Pale +3 | |
LMG197 #1839¥ | 27 | 20/60, 20/125 | 140, 15, 0 | 140, 15, 0 | Clear | ERM | RPE atrophy | Pale +1 |
37 | 20/125, 20/250 | 65, 13, 0 | 55, 10, 0 | Clear | ERM | Spicules | Pale +3 | |
52 | 20/250, 20/250 | 35, 12, 0 | 30, 4, 0 | PSC +1 | Atrophy | Spicules | Pale +3 |
Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
---|---|---|---|---|
Gene (mouse) | Pcdh15 | GenBank | Gene ID: 11994 | |
Gene (human) | PCDH15 | GenBank | Gene ID: 65217 | |
Genetic reagent (Mus musculus) | Pcdh15R250X | This paper | ||
Antibody | Protocadherin-15 (Rabbit polyclonal) | Ahmed et al., 2003a | PB303;C-terminus | IF (1:200) |
Antibody | Opsin (Ret-P1; mouse monoclonal) | MilliporeSigma | MAB5316 | IF (1:500) |
Antibody | Transducin (mouse monoclonal) | Santa Cruz Biotechnology | Sc-517057 | IF (1:100) |
Antibody | Arrestin(mouse monoclonal) | Drs. Paul Hargrave and Clay Smith, University of Florida, FA | clone C10C10 | IF (1:25) |
Antibody | Protocadherin-15(Rabbit polyclonal) | Ahmed et al., 2006 | HL5614;N-terminus | IF (1:1200) |
Antibody | Transducin(mouse monoclonal) | Santa Cruz Biotechnology | Sc-517057 | IF (1:100) |
Antibody | Rhodopsin clone RET-P1(mouse monoclonal) | EMD Millipore | MAB5316 | IF (1:250) |
Antibody | Actin clone 13E5(Rabbit polyclonal) | Cell Signaling Technology | 4970S | IF (1:200) |
Probe | Rhodamine phalloidin | Thermo Fisher Scientific | R415 | IF (1:200) |
Antibody | IRBP(Rabbit polyclonal) | Santa Cruz Biotechnology | Sc-25787 | WB (1:500) |
Antibody | CRALBP(Rabbit polyclonal) | Santa Cruz Biotechnology | Sc-28193 | WB (1:1000) |
Antibody | RPE65(Rabbit polyclonal) | Kind gift from Dr. Michael Redmond, National Institutes of Health, Bethesda, MD | – | WB (1:100) |
Chemical compound, drug | 9-cis retinal | Sigma-Aldrich | R5754 | |
Commercial assay or kit | ECL Prime Western Blotting System | Thermo Fisher Scientific | 32,106 | |
Other | FM1-43 | Thermo Fisher Scientific | T3163 | Dye |
Other | Chaps Hydrate ≥98% (HPLC) | Sigma-Aldrich | SIG-C3023-25G | Detergent |
Data for all figures and figure supplements.