title: Novel mutation in the gamma-S crystallin gene causing autosomal dominant cataract.
abstract: OBJECTIVE
  To identify the underlying genetic defect in a north Indian family with seven members in three-generations affected with bilateral congenital cataract.
  
  
  METHODS
  Detailed family history and clinical data were recorded. Linkage analysis using fluorescently labeled microsatellite markers for the already known candidate gene loci was performed in combination with mutation screening by bidirectional sequencing.
  
  
  RESULTS
  Affected individuals had bilateral congenital cataract. Cataract was of opalescent type with the central nuclear region denser than the periphery. Linkage was excluded for the known cataract candidate gene loci at 1p34-36, 1q21-25 (gap junction protein, alpha 8 [GJA8]), 2q33-36 (crystallin, gamma A [CRYGA], crystallin, gamma B [CRYGB], crystallin, gamma C [CRYGC], crystallin, gamma D [CRYGD], crystallin, beta A2 [CRYBA2]), 3q21-22 (beaded filament structural protein 2, phakinin [BFSP2]), 12q12-14 (aquaporin 0 [AQP0]), 13q11-13 (gap junction protein, alpha 3 [GJA3]), 15q21-22, 16q22-23 (v-maf musculoaponeurotic fibrosarcoma oncogene homolog [MAF], heat shock transcription factor 4 [HSF4]), 17q11-12 (crystallin, beta A1 [CRYBA1]), 17q24, 21q22.3 (crystallin, alpha A [CRYAA]), and 22q11.2 (crystallin, beta B1 [CRYBB1], crystallin, beta B2 [CRYBB2], crystallin, beta B3 [CRYBB3], crystallin, beta A4 [CRYBA4]). Crystallin, alpha B (CRYAB) at chromosome 11q23-24 was excluded by sequence analysis. However, sequencing the candidate gene, crystallin, gamma S (CRYGS), at chromosome 3q26.3-qter showed a heterozygous c.176G-->A change that resulted in the replacement of a structurally highly conserved valine by methionine at codon 42 (p.V42M). This sequence change was not observed in unaffected family members or in the 100 ethnically matched controls.
  
  
  CONCLUSIONS
  We report a novel missense mutation, p.V42M, in CRYGS associated with bilateral congenital cataract in a family of Indian origin. This is the third report of a mutation in this exceptional member of the beta-/gamma-crystallin superfamily and further substantiates the genetic and clinical heterogeneity of autosomal dominant cataract.
authors.affiliation: Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, India. vanita_kumar@yahoo.com
authors.forename: Vanita
authors.initials: V
authors.lastname: Vanita
authors.forename: Jai Rup
authors.initials: JR
authors.lastname: Singh
authors.forename: Daljit
authors.initials: D
authors.lastname: Singh
authors.forename: Raymonda
authors.initials: R
authors.lastname: Varon
authors.forename: Karl
authors.initials: K
authors.lastname: Sperling
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D016022:Case-Control Studies; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D002675:Child, Preschool; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007194:India; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D038222:gamma-Crystallins / Q000235:genetics*
chemical_list: D038222:gamma-Crystallins; C077648:CRYGS protein, human; D004247:DNA