title: The congenital "ant-egg" cataract phenotype is caused by a missense mutation in connexin46.
abstract: OBJECTIVE
  "Ant-egg" cataract is a rare, distinct variety of congenital/infantile cataract that was reported in a large Danish family in 1967. This cataract phenotype is characterized by ant-egg-like bodies embedded in the lens in a laminar configuration and is inherited as an autosomal dominant trait. We retrieved the family and performed linkage analysis to determine the disease locus and identify the mutated gene.
  
  
  METHODS
  The family (CC00103) was identified in a National Register of Hereditary Eye Diseases and updated based on The Danish Civil Register System. Genome wide linkage analysis and haplotyping using STS marker systems were carried out to achieve a LOD score above 3. The disease-causing candidate gene was sequenced and the mutation was identified and verified by restriction enzyme digestion of genomic DNA from all individuals in family CC00103 and 60 healthy controls.
  
  
  RESULTS
  Linkage analysis resulted in a LOD score of 3.91 for marker D13S1275 located close to the known cataract gene GJA3. A novel missense mutation c.32T > C (L11S), was found by sequencing DNA from two affected members. The mutation was present in all affected individuals and was neither found in unaffected family members nor in 60 healthy individuals by restriction enzyme digests.
  
  
  CONCLUSIONS
  The congenital "ant-egg" cataract phenotype is caused by a L11S mutation in connexin46 (Cx46) located in the signal peptide domain. Further studies are needed to unravel the mechanism leading to the formation of the "ant-eggs".
authors.affiliation: The Wilhelm Johannsen Centre for Functional Genome Research, Institute of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.forename: Wenliang
authors.initials: W
authors.lastname: Yao
authors.forename: Hans
authors.initials: H
authors.lastname: Eiberg
authors.forename: Mikkel
authors.initials: M
authors.lastname: Funding
authors.forename: Ruth
authors.initials: R
authors.lastname: Riise
authors.forename: Klaus Wilbrandt
authors.initials: KW
authors.lastname: Kjaer
authors.forename: James Fielding
authors.initials: JF
authors.lastname: Hejtmancik
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002386:Cataract / Q000235:genetics* / Q000473:pathology*; D017630:Connexins / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007930:Leucine; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D021382:Protein Sorting Signals / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012694:Serine
chemical_list: D017630:Connexins; D021382:Protein Sorting Signals; C082917:GJA3 protein, human; D012694:Serine; D007930:Leucine