To test patients from southern India for the presence of mutations that most commonly cause Leber congenital amaurosis (LCA) in northern America.
A review of the literature identified 177 unique LCA causing mutations in eight different genes: aryl hydrocarbon receptor interacting protein-like 1 ( AIPL1), crumbs homolog 1 ( CRB1), cone-rod homeobox ( CRX), guanylate cyclase 2D ( GUCY2D), nephronophthisis 6 ( NPHP6), retinol dehydrogenase 12 ( RDH12), retinal pigment epithelium-specific protein 65 kDa ( RPE65), and retinitis pigmentosa GTPase regulator interacting protein 1 ( RPGRIP1). Allele-specific ligation assay and bidirectional sequencing were used to test 38 unrelated LCA patients from southern India for 104 of these mutations, which contribute to more than 30% of the LCA cases in a northern American population.
Only one participant was found to harbor one of the 104 mutations in the allele-specific assay (homozygous RPE65 Tyr368His). A mutation that was not part of the assay (homozygous RPE65 Tyr143Asp) was incidentally detected in a second patient when an equivocal signal from one allele on the assay was followed up with automated DNA sequencing.
Mutations that contribute to 30% of the LCA cases in northern America were detected in only 2.6% of LCA cases in our cohort from southern India. There were no instances of IVS26 c.2991+1655 A>G in NPHP6, the most commonly detected mutation in LCA. These data suggest that LCA in India is caused primarily by a different set of mutations in the same genes associated with disease in northern America, or by mutations in other genes that have not yet been discovered. Therefore, mutation-specific assays developed for European and northern American cohorts may not be suited for testing LCA patients from India or other ethnically distinct populations.