Mutations in CEP78 consistently result in progressive cone-rod degeneration with variable age of onset and mild to severe deafness, which appeared to be stationary in the two subjects who were specifically tested for hearing loss. Clear inter-individual phenotypic variations have been observed.
Sign and symptoms may include:
- Visual impairment
- Nystagmus
- Photophobia
- Impaired color vision and/or dyschromatopsia
- Mild to severe hearing loss
- Absence of other systemic features
Overview of the literature on clinical characteristics of subjects harboring CEP78 mutations
The first study about mutations in CEP78 described three subjects: one from Greece and two from Sweden. The Greek subject (a 59 y.o. male) was from the island of Crete with hemarelopia since early adulthood (18–20 y.o.) with progression to severe central vision deficit (35-40 y.o.) and evolution into severe visual impairment, nystagmus, photophobia and dyschromatopsia. At first visit, fundus examination revealed minimal aberrations with normal color and normal vessels but a small atrophic foveal area with subjacent ring-like glistening in one eye and bull’s-eye maculopathy in the other eye. Full-field electroretinography (ERG) showed flat cone responses with residual rod-mediated signals. The subject also featured mild hearing deficit.
The Swedish subjects were siblings (a male and a female). They displayed retinal degeneration since childhood. Clinical evaluation at 69 and 65 years of age, respectively, featured visual problems, including loss of color sensitivity and of central vision. Both subjects had hearing deficits since early adulthood, suffering from substantial sensorineural hearing loss. Similar to the situation for the Greek subject, full-field ERG of both individuals highlighted almost no residual cone activity but still revealed some rod-mediated responses, even at advanced age.
In another study, including a cohort of Israeli and Palestinian families with inherited retinal degeneration, six affected individuals from five families presented with similar cone-dominated symptoms and accompanied by hearing loss with a variable age of onset (10-45 y.o.). ERG testing and audiometry tests confirmed the clinical picture of the subjects mentioned above.
Furthermore, two additional families from China displaying “atypical Usher Syndrome” have also been reported. In the first family, a 33-year-old woman and her older sister featured progressive vision loss (onset of symptoms: 13 y.o.) with photophobia, impaired color vision and late hearing loss. In the second family, the proband was reported with developed night blindness, hypochromatopsia and mild hearing loss since early childhood. She suffered from visual field decrease and central vision loss since the age of 10 years. The proband had also has an affected brother with similar ophthalmological findings as well as hearing loss.
Finally, a 66-year-old male from the United Kingdom with a cone-rod degeneration and hearing loss was recently identified to harbour a homozygous deletion-inversion-deletion overlapping CEP78. This patient’s symptoms begun during his fifth decade, with central vision loss, photophobia and nystagmus accompanied by progressive hearing impairment, following a severe influenza-like viral infection. On the molecular level, two homozygous deletions in chromosome 9 of nearly 6 and 10 Kb were found flanking an inversion of 298 bp with the second deletion intersecting the first 5 exons of CEP78.