title: A novel deletion mutation in proteoglycan-4 underlies camptodactyly-arthropathy-coxa-vara-pericarditis syndrome in a consanguineous pakistani family.
abstract: OBJECTIVE
  Camptodactyly-arthropathy-coxa-vara-pericarditis (CACP) syndrome is an autosomal recessive condition that mostly affects joints and tendons but can also affect the pericardium, which is a surface surrounding the heart. CACP syndrome is caused by mutations in a secreted proteoglycan 4 (PRG4) gene, which expresses in skeletal as well as nonskeletal tissues. We undertook this study to genetically screen a large consanguineous Pakistani family segregating CACP in an autosomal recessive manner.
  
  
  METHODS
  Genome-wide homozygosity mapping of 10 members of a Pakistani family including six affected and four normal individuals was carried out using 250K SNP genotyping array. To screen for mutation in PRG4 gene, all coding exons and exon-intron junctions were sequenced using ABI prism 3730 automated DNA sequencer.
  
  
  RESULTS
  Genome-wide homozygosity mapping revealed a large homozygous region on chromosome 1 carried by all the affected individuals. This region contains the previously described PRG4 gene involved in CACP syndrome. Sequence analysis of PRG4 gene in affected individuals of the family presented here revealed a 2 base-pair (bp) deletion (c.2816_2817delAA) predicting a frame shift mutation (p.Lys939fsX38). To our knowledge, this is probably the first mutation identified in PRG4 gene in a Pakistani family.
  
  
  CONCLUSIONS
  We described a 2-bp novel deletion mutation in PRG4 gene in a Pakistani family with CACP. Our findings extend the body of evidence that only nonsense mutation in PRG4 gene triggers the phenotype.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan.
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.forename: Zafar
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Masha
authors.initials: M
authors.lastname: Umicevic-Mirkov
authors.forename: Syed
authors.initials: S
authors.lastname: Kamran Ul-Hassan Naqvi
authors.forename: Marieke
authors.initials: M
authors.lastname: Coenen
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D001177:Arthropathy, Neurogenic / Q000235:genetics*; D001483:Base Sequence; D003241:Consanguinity; D060905:Coxa Vara; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D005838:Genotype; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006801:Humans; D010154:Pakistan; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D013585:Synovitis / Q000235:genetics*; D000099158:Proteoglycan 4
chemical_list: D011509:Proteoglycans; C419197:PRG4 protein, human; D000099158:Proteoglycan 4