1. Mutations that are a common cause of Leber congenital amaurosis in northern America are rare in southern India.
- Author
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Sundaresan P, Vijayalakshmi P, Thompson S, Ko AC, Fingert JH, and Stone EM
- Subjects
- Adolescent, Adult, Alleles, Child, Child, Preschool, DNA Mutational Analysis, Family, Female, Genotype, Humans, India, Infant, Male, North America, Pedigree, Blindness complications, Blindness genetics, Mutation genetics, Optic Atrophy, Hereditary, Leber complications, Optic Atrophy, Hereditary, Leber genetics
- Abstract
Purpose: To test patients from southern India for the presence of mutations that most commonly cause Leber congenital amaurosis (LCA) in northern America., Methods: 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., Results: 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., Conclusions: 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.
- Published
- 2009