title: Mutations that are a common cause of Leber congenital amaurosis in northern America are rare in southern India.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Genetics, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Madurai, Tamilnadu, India.
authors.forename: Periasamy
authors.initials: P
authors.lastname: Sundaresan
authors.forename: P
authors.initials: P
authors.lastname: Vijayalakshmi
authors.forename: Stewart
authors.initials: S
authors.lastname: Thompson
authors.forename: Audrey C
authors.initials: AC
authors.lastname: Ko
authors.forename: John H
authors.initials: JH
authors.lastname: Fingert
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001766:Blindness / Q000150:complications* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D009656:North America; D029242:Optic Atrophy, Hereditary, Leber / Q000150:complications* / Q000235:genetics*; D010375:Pedigree