title: Mutational analysis and genotype-phenotype correlations in southern Indian patients with sporadic and familial aniridia.
abstract: OBJECTIVE
  Aniridia is a rare panocular disorder characterized by iris hypoplasia and other associated eye anomalies. Heterozygous null mutations in paired box gene 6 (PAX6) are the major cause of the classic aniridia phenotype. This study aims to detect the mutational spectrum of PAX6 and associated phenotypes in southern Indian patients with sporadic and familial aniridia.
  
  
  METHODS
  Genomic DNA was isolated from peripheral blood from all participants. The coding regions and flanking intronic sequences of PAX6 were screened with Sanger sequencing in 30 probands with aniridia. The identified variations were further evaluated in available family members and 150 healthy controls. The pathogenic potential of the mutations were assessed using bioinformatics tools.
  
  
  RESULTS
  Thirteen different mutations were detected in eight sporadic and five familial cases. Eleven novel mutations, including five insertions (c.7_10dupAACA, c.567dupC, c.704dupC, c.868dupA and c.753_754insTA), two deletions (c.242delC and c.249delT), and four splicing variants (c.10+1G>A, c.141G>A, c.141+4A>G and c.764A>G) were identified in this study. Clinical findings of the patients revealed phenotypic heterogeneity with the same or different mutations.
  
  
  CONCLUSIONS
  This study reported 11 novel mutations and thus expanded the spectrum of PAX6 mutations. Interestingly, all mutations reported in this study were truncations, which confirms the hypothesis that haploinsufficiency of PAX6 causes the aniridia phenotype. Our observations revealed inter- and intrafamilial phenotypic variability with PAX6 mutations. The common ocular findings associated with PAX6 mutations were iris hypoplasia, nystagmus, and foveal hypoplasia reported in almost all cases, with cataract, glaucoma, and keratopathy reported in approximately 50% of the patients.
authors: Department of Genetics, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Madurai, India.
authors: Sushil Kumar
authors: SK
authors: Dubey
authors: Department of Genetics, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Madurai, India.
authors: Nagasubramanian
authors: N
authors: Mahalaxmi
authors: Department of Pediatric Ophthalmology and Strabismus, Aravind Eye Hospital, Madurai, India.
authors: Perumalsamy
authors: P
authors: Vijayalakshmi
authors: Department of Genetics, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Madurai, India.
authors: Periasamy
authors: P
authors: Sundaresan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015783:Aniridia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D016022:Case-Control Studies; D002386:Cataract / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005584:Fovea Centralis / Q000002:abnormalities* / Q000473:pathology; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D005901:Glaucoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D057895:Haploinsufficiency; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D007438:Introns; D007498:Iris / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020417:Nystagmus, Congenital / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009759:Nystagmus, Pathologic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016366:Open Reading Frames; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012164:Retinal Diseases / Q000150:complications / Q000151:congenital* / Q000235:genetics / Q000473:pathology
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins