Tina Lamey, Terri McLaren, Hannah Montgomery,Ling Hoffmann, Caitlyn Kap, John De Roach

Purpose:
To identify the genetic cause for diseasein Australians clinically diagnosed with LCA. Assubtleties of the LCA phenotype are gene-specific,identifying the genetic cause may assist patient man-agement. Moreover, the genes RPE65 and AIPL1 wereof particular interest owing to the potential for partici-pant referral to gene-specific clinical trials.

Methods:
Subjects were sourced from the AustralianInherited Retinal Disease Register and DNA Bank(AIRDR). Proband DNA from 20 families was analysedby LCA genotyping microarray. Where no mutationswere identified, RPE65 and AIPL1 were directlysequenced.

Results:
Microarray analysis resulted in identificationof one mutation in eight cases. CEP-290 and CRB1were implicated as the likely disease-causing genes inthree and two cases respectively. GUCY2D, RPGRIP1and SPATA7 were implicated in one family each.RPE65 and AIPL were sequenced in the remaining 12samples. In one proband, two novel pathogenic RPE65variants were identified.

Conclusion:
For the first time in an Australian clini-cally diagnosed with LCA/RP, RPE65 has been identi-fied as the disease-causing gene. These mutations werenot detected by microarray as they are novel. Thisemphasises the importance of undertaking the rela-tively inexpensive practice of sequencing the RPE65gene in patients diagnosed with LCA. The RPE65-LCAphenotype is generally less severe than that caused byother LCA genes. Combined with that LCA is under-represented in the AIRDR, it is possible that moreRPE65 cases will be identified by screening probandsin the RP cohort where age onset is less than five yearsof age.