title: A novel splice-site mutation in the CDH3 gene in hypotrichosis with juvenile macular dystrophy.
abstract: BACKGROUND
  Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse hair on the scalp and early blindness. Mutations in the CDH3 gene have been reported to underlie HJMD.
  
  
  OBJECTIVE
  To identify a gene responsible for HJMD in a large, four-generation Pakistani family.
  
  
  METHODS
  Genotyping of 13 members of the family, including 6 affected and 7 unaffected members, was carried out using polymorphic microsatellite markers closely linked to the CDH3 on chromosome 16q22.1. To screen for mutations in the CDH3 gene, all of its exons and splice junctions were amplified using PCR from genomic DNA and sequenced directly, using an automated DNA sequencer.
  
  
  RESULTS
  Microsatellite analysis showed linkage of the family to the CDH3 gene on chromosome 16q22.1. Sequence analysis of the CDH3 gene revealed a novel splice-site mutation (IVS10-1 G-->T), leading to probable skipping of exon 11 and a shift in the reading frame.
  
  
  CONCLUSIONS
  The mutation identified here represents the first mutation in the CDH3 gene causing HJMD in a Pakistani population.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: M
authors.initials: M
authors.lastname: Jelani
authors.forename: M
authors.initials: M
authors.lastname: Salman Chishti
authors.forename: W
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D015820:Cadherins / Q000235:genetics*; D002648:Child; D003241:Consanguinity; D003317:Corneal Dystrophies, Hereditary / Q000150:complications / Q000235:genetics*; D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007039:Hypotrichosis / Q000150:complications / Q000235:genetics*; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D055815:Young Adult
chemical_list: C512197:CDH3 protein, human; D015820:Cadherins