title: A new betaA1-crystallin splice junction mutation in autosomal dominant cataract.
abstract: OBJECTIVE
  To map the locus for autosomal dominant cataracts (ADCs) in a Brazilian family using candidate gene linkage analyses, describe the clinical variability, and identify potential mutations in the human betaA1-crystallin gene (CRYBA1), a candidate gene identified through linkage studies demonstrating cosegregation with markers on chromosome 17.
  
  
  METHODS
  Members of a Brazilian family with ADC were studied. Clinical examinations and linkage analyses with polymerase chain reaction (PCR) polymorphisms of 22 anonymous markers and 2 within the neurofibromatosis type 1 gene were performed; two-point lod scores were calculated. DNA sequences of all 6 exons and 12 exon-intron boundaries of the betaA1-crystallin gene, a proximal candidate gene mapped to 17q11.1-q12 in one unaffected and two affected individuals, were screened and new variants assessed for cosegregation with the disease.
  
  
  RESULTS
  Affected individuals exhibited variable expressivity of pulverulent opacities in the embryonal nucleus and sutures; star-shaped, shieldlike, or radial opacities in the posterior embryonal nucleus; and/or midcortical opacities. All known loci for ADC in this family on chromosomes 1 and 13 were excluded. A positive lod score on chromosome 17 was calculated. This ADC locus was mapped to two potential regions on the long arm with an intervening recombination. The only known candidate gene in these regions was betaA1-crystallin. Three previously unreported single nucleotide variants were found in this gene, one in the donor splice junction site of intron C. This variant was found in all affected members and is presumed to be the causative mutation.
  
  
  CONCLUSIONS
  An ADC locus was mapped in a Brazilian family with variable expressivity to either 17q23.1-23.2 or 17q11.1-12 based on linkage analyses. Analyses of DNA sequences of the betaA1-crystallin gene in this family revealed three new variants, one of which is within a donor splice junction and cosegregates with affected members.
authors.affiliation: Departments of Ophthalmology, The Children's Hospital, the University of Colorado School of Medicine, Denver, Colorado 80264, USA. bronwyn.bateman@uchsc.edu
authors.forename: J B
authors.initials: JB
authors.lastname: Bateman
authors.forename: D D
authors.initials: DD
authors.lastname: Geyer
authors.forename: P
authors.initials: P
authors.lastname: Flodman
authors.forename: M
authors.initials: M
authors.lastname: Johannes
authors.forename: J
authors.initials: J
authors.lastname: Sikela
authors.forename: N
authors.initials: N
authors.lastname: Walter
authors.forename: A T
authors.initials: AT
authors.lastname: Moreira
authors.forename: K
authors.initials: K
authors.lastname: Clancy
authors.forename: M A
authors.initials: MA
authors.lastname: Spence
mesh_terms: D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003459:Crystallins / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D015785:Eye Diseases, Hereditary / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012326:RNA Splicing / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D003459:Crystallins; D017931:DNA Primers; D005819:Genetic Markers