Purpose. 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 new shown to be pathogenic when mutated.
|Original language||English (US)|
|Number of pages||10|
|Journal||Investigative Ophthalmology and Visual Science|
|Publication status||Published - 2000|
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