HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model.
OBJECTIVE
To investigate the function and pathogenicity of HRG4, a photoreceptor synaptic protein homologous to the Caenorhabditis elegans neuroprotein UNC119.


METHODS
HRG4 was screened for mutations in patients with various retinopathies, and a transgenic mouse model was constructed and analyzed based on a mutation found.


RESULTS
A heterozygous premature termination codon mutation was found in a 57-year-old woman with late-onset cone-rod dystrophy. In some transgenic mice carrying the identical mutation, age-dependent fundus lesions developed accompanied by electroretinographic changes consistent with defects in photoreceptor synaptic transmission (depressed b-wave, normal c-wave), and retinal degeneration occurred with marked synaptic and possible transsynaptic degeneration.


CONCLUSIONS
HRG4, the only synaptic protein known to be highly enriched in photoreceptor ribbon synapses, is now shown to be pathogenic when mutated.
Kobayashi
A
A
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Florida, USA.
Higashide
T
T
Hamasaki
D
D
Kubota
S
S
Sakuma
H
H
An
W
W
Fujimaki
T
T
McLaren
M J
MJ
Weleber
R G
RG
Inana
G
G
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D004195:Disease Models, Animal; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology* / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014794:Visual Fields
D048868:Adaptor Proteins, Signal Transducing; D005136:Eye Proteins; C098032:UNC119 protein, human