Gene medicine aims to utilize genomic information about patients to facilitate treatment. Gene therapy and regenerative therapy for ophthalmic inherited disorders is becoming a clinical reality. A necessary precursor to these new therapies is accurate molecular diagnosis of the mutation (s) underlying a disease. I review the gene by gene analysis with Sanger sequencing and DNA microarray re-sequencing methods to obtain a diagnosis and identify disease causing gene mutations for inherited optic nerve atrophy and retinal degenerative diseases. In most situations, the gene by gene analysis proved too laborious. The DNA microarray re-sequencing seems to be a rapid method for detecting mutations in patients with genetically heterogeneous diseases such as Leber's congenital amaurosis (LCA) and retinitis pigmentosa (RP). In this study, the responsible mutations were identified in three of 11 pedigrees of LCA. Next-generation sequencing based diagnosis may offer several advantages over microarray-based methods. However, the relative difficulty of interpreting sequence results and the development of reliable bioinformatic tools remain outstanding concerns. Finally, I discuss ways of conducting genetic counseling of issues with massive genome analysis in the new era of gene medicine.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 118: 283-298, 2014.