Purpose: To describe the phenotype in a New Zealand family with an unusual severe X-linked retinal disorder with a novel I745T mutation in CACNA1F, the gene responsible for incomplete congenital stationary night blindness (CSNB2).
Methods: Members of the family tree were invited for clinical, psychophysical and electrodiagnostic evaluation.
Results: Male family members had severe non-progressive visual impairment, abnormal colour vision, congenital nystagmus, hyperopia and normal fundi. Some were intellectually disabled. Female family members had congenital nystagmus and decreased visual acuity frequently associated with high myopia. Electroretinograms (ERG) identified reduced rod and cone responses with negative waveform in male and female family members, with atypical features for CSNB2.
Conclusions: Although there were similarities to CSNB2, distinctive features in male family members included severity of phenotype, and association of intellectual disability. Moreover, all female heterozygotes had clinical and ERG abnormalities. CACNA1F encodes the Cav1.4 α1 subunit of a voltage-gated calcium channel, which may mediate neurotransmitter release from photoreceptors. Molecular analyses, reported separately, identified a novel I745T CACNA1F mutation that was associated in vitro with major alterations in gating and kinetics of the Cav1.4 channel. It is speculated that the unique phenotype described in this family may reflect similarly altered function of Cav1.4 channel activity in vivo.