title: Posterior polar cataract: genetic analysis of a large family.
abstract: Congenital cataracts are clinically and genetically heterogeneous. Loci for autosomal dominant posterior polar cataracts have been mapped to chromosomes 1p36, 11q22-q22.3, 16q22, and 20p12-q12. We investigated a large four-generation family with 20 individuals affected with congenital posterior polar cataracts. After exclusion of known loci for posterior polar cataracts, a genome-wide screen was conducted. In this family, we mapped dominant congenital posterior polar cataracts to chromosome 10q24. On haplotype analysis, we identified an 11-cM interval between loci D10S1680 and D10S467, which included the PITX3 gene. On sequencing the coding region of PITX3, we found a 17-base-pair duplication in exon 4. Although the same genotype was described in a family with ASMD and cataracts, the common phenotype of this mutation is probably posterior polar cataract; a modifier gene is presumed to cause anterior segment abnormalities in the previously described patients. The same mutation was recently identified in four families with congenital cataracts. This study provides further evidence of genetic heterogeneity of autosomal dominant posterior polar cataract.
authors.affiliation: The Johns Hopkins Service for Hereditary Eye Diseases, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Finzi
authors.forename: Yingying
authors.initials: Y
authors.lastname: Li
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Mitchell
authors.forename: Arman
authors.initials: A
authors.lastname: Farr
authors.forename: Irene H
authors.initials: IH
authors.lastname: Maumenee
authors.forename: Juliana M F
authors.initials: JM
authors.lastname: Sallum
authors.forename: Olof
authors.initials: O
authors.lastname: Sundin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002386:Cataract / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020440:Gene Duplication; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C433629:homeobox protein PITX3