title: A novel insertion mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene underlies Grebe-type chondrodysplasia in a consanguineous Pakistani family.
abstract: BACKGROUND
  Grebe-type chondrodysplasia (GCD) is a rare autosomal recessive syndrome characterized by severe acromesomelic limb shortness with non-functional knob like fingers resembling toes. Mutations in the cartilage-derived morphogenetic protein 1 (CDMP1) gene cause Grebe-type chondrodysplasia.
  
  
  METHODS
  Genotyping of six members of a Pakistani family with Grebe-type chondrodysplasia, including two affected and four unaffected individuals, was carried out by using polymorphic microsatellite markers, which are closely linked to CDMP1 locus on chromosome 20q11.22. To screen for a mutation in CDMP1 gene, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected and unaffected individuals of the family and sequenced directly in an ABI Prism 310 automated DNA sequencer.
  
  
  RESULTS
  Genotyping results showed linkage of the family to CDMP1 locus. Sequence analysis of the CDMP1 gene identified a novel four bases insertion mutation (1114insGAGT) in exon 2 of the gene causing frameshift and premature termination of the polypeptide.
  
  
  CONCLUSIONS
  We describe a 4 bp novel insertion mutation in CDMP1 gene in a Pakistani family with Grebe-type chondrodysplasia. Our findings extend the body of evidence that supports the importance of CDMP1 in the development of limbs.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan. biochemistsulfi@yahoo.com
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.forename: Syed Kamran-ul-Hassan
authors.initials: SK
authors.lastname: Naqvi
authors.forename: Naveed
authors.initials: N
authors.lastname: Wasif
authors.forename: Ghazanfar
authors.initials: G
authors.lastname: Ali
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D002648:Child; D002890:Chromosomes, Human, Pair 20; D003241:Consanguinity; D005260:Female; D005532:Foot Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D005808:Genes, Recessive; D005838:Genotype; D055428:Growth Differentiation Factor 5 / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D016254:Mutagenesis, Insertional; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D011859:Radiography; D017422:Sequence Analysis, DNA
chemical_list: C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5