title: Refinement of the X-linked cataract locus (CXN) and gene analysis for CXN and Nance-Horan syndrome (NHS).
abstract: The X-linked congenital cataract (CXN) locus has been mapped to a 3-cM (approximately 3.5 Mb) interval on chromosome Xp22.13, which is syntenic to the mouse cataract disease locus Xcat and encompasses the recently refined Nance-Horan syndrome (NHS) locus. A positional cloning strategy has been adopted to identify the causative gene. In an attempt to refine the CXN locus, seven microsatellites were analysed within 21 individuals of a CXN family. Haplotypes were reconstructed confirming disease segregation with markers on Xp22.13. In addition, a proximal cross-over was observed between markers S3 and S4, thereby refining the CXN disease interval by approximately 400 Kb to 3.2 Mb, flanked by markers DXS9902 and S4. Two known genes (RAI2 and RBBP7) and a novel gene (TL1) were screened for mutations within an affected male from the CXN family and an NHS family by direct sequencing of coding exons and intron- exon splice sites. No mutations or polymorphisms were identified, therefore excluding them as disease-causative in CXN and NHS. In conclusion, the CXN locus has been successfully refined and excludes PPEF1 as a candidate gene. A further three candidates were excluded based on sequence analysis. Future positional cloning efforts will focus on the region of overlap between CXN, Xcat, and NHS.
authors.affiliation: Division of Molecular Genetics Institute of Ophthalmology 11-43 Bath Street London EC1V 9EL UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Brooks
authors.forename: Neil
authors.initials: N
authors.lastname: Ebenezer
authors.forename: Subathra
authors.initials: S
authors.lastname: Poopalasundaram
authors.forename: Eamonn
authors.initials: E
authors.lastname: Maher
authors.forename: Peter
authors.initials: P
authors.lastname: Francis
authors.forename: Anthony
authors.initials: A
authors.lastname: Moore
authors.forename: Alison
authors.initials: A
authors.lastname: Hardcastle
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002874:Chromosome Mapping; D020090:Chromosome Segregation; D041321:Chromosomes, Human, X; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D018895:Microsatellite Repeats; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012326:RNA Splicing; D056524:Retinoblastoma-Binding Protein 7; D013577:Syndrome; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C488621:NHS protein, human; D009687:Nuclear Proteins; D011506:Proteins; C118924:RAI2 protein, human; C490746:RBBP7 protein, human; D056524:Retinoblastoma-Binding Protein 7; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha; C107424:PPEF1 protein, human; D010749:Phosphoprotein Phosphatases