title: A nonsense mutation in the glucosaminyl (N-acetyl) transferase 2 gene (GCNT2): association with autosomal recessive congenital cataracts.
abstract: OBJECTIVE
  To identify the genetic defect associated with autosomal recessive congenital cataract in four Arab families from Israel.
  
  
  METHODS
  Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point lod scores were calculated using MLINK of the LINKAGE program package. Mutation analysis of the glucosaminyl (N-acetyl) transferase 2 gene (GCNT2) gene was performed by direct sequencing of PCR-amplified exons.
  
  
  RESULTS
  The cataract locus was mapped to a 13.0-cM interval between D6S470 and D6S289 on Chr. 6p24. A maximum two-point lod score of 8.75 at theta = 0.019 was obtained with marker D6S470. Sequencing exons of the GCNT2 gene, mutations of which have been associated with cataracts and the i blood group phenotype, revealed in these families a homozygous G-->A substitution in base 58 of exon-2, resulting in the formation of premature stop codons W328X, W326X, and W328X, of the GCNT2A, -B, and -C isoforms, respectively. Subsequent blood typing of affected family members confirmed the possession of the rare adult i blood group phenotype.
  
  
  CONCLUSIONS
  A nonsense mutation in the GCNT2 gene isoforms is associated with autosomal recessive congenital cataract in four distantly related Arab families from Israel. These findings provide further insight into the dual role of the I-branching GCNT2 gene in the lens and in reticulocytes.
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1860, USA.
authors.forename: Eran
authors.initials: E
authors.lastname: Pras
authors.forename: Judith
authors.initials: J
authors.lastname: Raz
authors.forename: Vered
authors.initials: V
authors.lastname: Yahalom
authors.forename: Moshe
authors.initials: M
authors.lastname: Frydman
authors.forename: Hanna J
authors.initials: HJ
authors.lastname: Garzozi
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
mesh_terms: D018912:Arabs / Q000208:ethnology; D002386:Cataract / Q000097:blood / Q000151:congenital* / Q000201:enzymology; D018389:Codon, Nonsense; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005820:Genetic Testing; D006801:Humans; D007048:I Blood-Group System / Q000032:analysis; D007527:Isoenzymes / Q000235:genetics; D007557:Israel / Q000453:epidemiology; D008126:Lod Score; D008297:Male; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D018389:Codon, Nonsense; D007048:I Blood-Group System; D007527:Isoenzymes; D017351:N-Acetylglucosaminyltransferases; C063312:beta-1,3-galactosyl-0-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase