title: CRYBB1 mutation associated with congenital cataract and microcornea.
abstract: OBJECTIVE
  The molecular characterization of a UK family with an autosomal dominant congenital cataract associated with microcornea is reported.
  
  
  METHODS
  Family history and clinical data were recorded. This phenotype was linked to a 7.6 cM region of chromosome 22q11.2-q12.2, spanning the beta-crystallin gene cluster (ZMax of 3.91 for marker D22S1114 at theta=0). Candidate genes were PCR amplified and screened for mutations on both strands using direct sequencing.
  
  
  RESULTS
  Sequencing of the coding regions and flanking intronic sequences of CRYBB2 and CRYBB1 showed the presence of a novel, heterozygous X253R change in exon 6 of CRYBB1. SSCP analysis confirmed that this sequence change segregated with the disease phenotype in all available family members and was not found in 109 ethnically matched controls.
  
  
  CONCLUSIONS
  X253R is predicted to elongate the COOH-terminal extension of the protein and would be expected to disrupt beta-crystallin interactions. This is the first documented involvement of CRYBB1 in ocular development beyond cataractogenesis.
authors.affiliation: Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Canada. c.willoughby@qub.ac.uk
authors.forename: Colin E
authors.initials: CE
authors.lastname: Willoughby
authors.forename: Ayad
authors.initials: A
authors.lastname: Shafiq
authors.forename: Walter
authors.initials: W
authors.lastname: Ferrini
authors.forename: Louie Loh Yen
authors.initials: LL
authors.lastname: Chan
authors.forename: Gail
authors.initials: G
authors.lastname: Billingsley
authors.forename: Megan
authors.initials: M
authors.lastname: Priston
authors.forename: Calvin
authors.initials: C
authors.lastname: Mok
authors.forename: Arvind
authors.initials: A
authors.lastname: Chandna
authors.forename: Stephen
authors.initials: S
authors.lastname: Kaye
authors.forename: Elise
authors.initials: E
authors.lastname: Héon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002386:Cataract / Q000151:congenital*; D002648:Child; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003315:Cornea / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D038206:beta-Crystallin B Chain / Q000235:genetics*
chemical_list: C105601:CRYBB1 protein, human; D038206:beta-Crystallin B Chain