title: Crystallin gene mutations in Indian families with inherited pediatric cataract.
abstract: OBJECTIVE
  Pediatric cataract is the most common form of treatable childhood blindness and is both clinically and genetically heterogeneous. Autosomal dominant and recessive forms of cataract have been reported to be caused by mutations in 22 different genes so far. Of the cataract mutations reported to date, about half the mutations occur in crystallins, a quarter of the mutations in connexins, and the remainder is evenly divided between intrinsic membrane proteins, intermediate filament proteins, and transcription factors. This study is aimed at identification of the spectrum and frequency of crystallin gene mutations in cataractous patients in an Indian population.
  
  
  METHODS
  Genetic analysis was extended to screen the entire coding region of the CRYAA, CRYAB, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD, and CRYGS genes using single stranded conformational polymorphism (SSCP) analysis as a screening technique followed by direct sequencing of all subjects that displayed an electrophoretic shift.
  
  
  RESULTS
  This report describes the first simultaneous mutation analysis of 10 crystallin genes in the same population, represented by 60 south Indian families. The analysis allowed the identification of causative mutations in 10 of the families (three novel and six reported). This includes six missense mutations (CRYAA-R12C, R21W, R54C, CRYAB- A171T, CRYGC-R168W, CRYGS- S39C), two nonsense mutations (CRYBB2- Q155X, CRYGD- R140X), and one splice mutation, which was identified in two families (CRYBA1-IVS3+1G>A).
  
  
  CONCLUSIONS
  Crystallin mutations are responsible for 16.6% of the inherited pediatric cataract in this population. As causative mutations have not been found in many of the families analyzed, this study suggests the presence of further novel genes or sequence elements involved in the pathogenesis of cataract in these families.
authors.affiliation: Department of Genetics, Dr. G. Venketaswamy Eye Research Institute, Aravind Medical Research Foundation, Aravind Eye Hospital, Madurai, India.
authors.forename: Ramachandran Ramya
authors.initials: RR
authors.lastname: Devi
authors.forename: Wenliang
authors.initials: W
authors.lastname: Yao
authors.forename: Perumalsamy
authors.initials: P
authors.lastname: Vijayalakshmi
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Sergeev
authors.forename: Periasamy
authors.initials: P
authors.lastname: Sundaresan
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017630:Connexins / Q000235:genetics; D003459:Crystallins / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D006801:Humans; D007194:India; D007231:Infant, Newborn; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D016415:Sequence Alignment
chemical_list: D017630:Connexins; D003459:Crystallins