title: PAX6 gene variations associated with aniridia in south India.
abstract: BACKGROUND
  Mutations in the transcription factor gene PAX6 have been shown to be the cause of the aniridia phenotype. The purpose of this study was to analyze patients with aniridia to uncover PAX6 gene mutations in south Indian population.
  
  
  METHODS
  Total genomic DNA was isolated from peripheral blood of twenty-eight members of six clinically diagnosed aniridia families and 60 normal healthy controls. The coding exons of the human PAX6 gene were amplified by PCR and allele specific variations were detected by single strand conformation polymorphism (SSCP) followed by automated sequencing.
  
  
  RESULTS
  The sequencing results revealed novel PAX6 mutations in three patients with sporadic aniridia: c.715ins5, [c.1201delA; c.1239A>G] and c.901delA. Two previously reported nonsense mutations were also found: c.482C>A, c.830G>A. A neutral polymorphism was detected (IVS9-12C>T) at the boundary of intron 9 and exon 10. The two nonsense mutations found in the coding region of human PAX6 gene are reported for the first time in the south Indian population.
  
  
  CONCLUSIONS
  The genetic analysis confirms that haploinsuffiency of the PAX6 gene causes the classic aniridia phenotype. Most of the point mutations detected in our study results in stop codons. Here we add three novel PAX6 gene mutations in south Indian population to the existing spectrum of mutations, which is not a well-studied ethnic group. Our study supports the hypothesis that a mutation in the PAX6 gene correlates with expression of aniridia.
authors.affiliation: Department of Genetics, Aravind Medical Research Foundation, Madurai, India. neethirajan@aravind.org
authors.forename: Guruswamy
authors.initials: G
authors.lastname: Neethirajan
authors.forename: Subbaiah Ramasamy
authors.initials: SR
authors.lastname: Krishnadas
authors.forename: Perumalsamy
authors.initials: P
authors.lastname: Vijayalakshmi
authors.forename: Shetty
authors.initials: S
authors.lastname: Shashikant
authors.forename: Periasamy
authors.initials: P
authors.lastname: Sundaresan
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015783:Aniridia / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005136:Eye Proteins; D005192:Family Health; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012097:Repressor Proteins
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D004247:DNA