title: Molecular and structural analysis of genetic variations in congenital cataract.
abstract: OBJECTIVE
  To determine the relative contributions of mutations in congenital cataract cases in an Indian population by systematic screening of genes associated with cataract.
  
  
  METHODS
  We enrolled 100 congenital cataract cases presenting at the Dr. R. P. Centre for Ophthalmic Sciences, a tertiary research and referral hospital (AIIMS, New Delhi, India). Crystallin, alpha A (CRYAA), CRYAB, CRYGs, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, beaded filament structural protein 1 (BFSP1), gap function protein, alpha 3 (GJA3), GJA8, and heat shock transcription factor 4 gene genes were amplified. Protein structure differences analysis was performed using Discovery Studio (DS) 2.0.
  
  
  RESULTS
  The mean age of the patients was 17.45±16.51 months, and the age of onset was 1.618±0.7181 months. Sequencing analysis of 14 genes identified 18 nucleotide variations. Fourteen variations were found in the crystallin genes, one in Cx-46 (GJA3), and three in BFSP1.
  
  
  CONCLUSIONS
  Congenital cataract shows marked clinical and genetic heterogeneity. Five nucleotide variations (CRYBA4:p.Y67N, CRYBB1:p.D85N, CRYBB1:p.E75K, CRYBB1:p.E155K, and GJA3:p.M1V) were predicted to be pathogenic. Variants in other genes might also be involved in maintaining lens development, growth, and transparency. The study confirms that the crystallin beta cluster on chromosome 22, Cx-46, and BFSP1 plays a major role in maintaining lens transparency. This study also expands the mutation spectrum of the genes associated with congenital cataract.
authors: Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
authors: Manoj
authors: M
authors: Kumar
authors: Tushar
authors: T
authors: Agarwal
authors: Punit
authors: P
authors: Kaur
authors: Manoj
authors: M
authors: Kumar
authors: Sudarshan
authors: S
authors: Khokhar
authors: Rima
authors: R
authors: Dada
mesh_terms: D002386:Cataract / Q000151:congenital / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D002892:Chromosomes, Human, Pair 22; D017630:Connexins / Q000235:genetics*; D003459:Crystallins / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D056426:Genetic Loci; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D007381:Intermediate Filament Proteins / Q000235:genetics*; D007438:Introns; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology; D008297:Male; D008958:Models, Molecular; D005810:Multigene Family; D009154:Mutation; D017422:Sequence Analysis, DNA; D044465:White People
chemical_list: D017630:Connexins; D003459:Crystallins; D005136:Eye Proteins; D007381:Intermediate Filament Proteins; C082917:GJA3 protein, human; C079098:filensin