title: Whole exome sequencing identified a novel zinc-finger gene ZNF141 associated with autosomal recessive postaxial polydactyly type A.
abstract: BACKGROUND
  Postaxial polydactyly (PAP) type A is characterised by well-formed functionally developed 5th digit duplication in hands and/or feet. It is genetically heterogeneous condition, inherited both in autosomal recessive and dominant manners. To date one autosomal recessive and four autosomal dominant loci have been mapped on human chromosomes. In the present study we have investigated a consanguineous Pakistani family segregating autosomal recessive PAP type A to identify the gene responsible for this phenotype.
  
  
  METHODS
  Whole exome sequencing combined with homozygosity mapping and array comparative genomic hybridisation (aCGH) analysis was used to search for a genetic cause of PAP type A in the present study.
  
  
  RESULTS
  Exome sequencing identified a missense mutation (c.1420C>T; p.Thr474Ile) in all the affected individuals of the family, in the gene ZNF141, mapped to the telomeric region on chromosome 4p16.3.
  
  
  CONCLUSIONS
  This study revealed involvement of a zinc finger gene ZNF141 in causing autosomal recessive PAP type A, which may open up interesting perspectives into the function of this protein in limb development.
authors.affiliation: Department of Biochemistry, Quaid-i-Azam University Islamabad, Islamabad, Pakistan.
authors.forename: Umm-e-
authors.initials: UE
authors.lastname: Kalsoom
authors.forename: Eva
authors.initials: E
authors.lastname: Klopocki
authors.forename: Naveed
authors.initials: N
authors.lastname: Wasif
authors.forename: Muhammad
authors.initials: M
authors.lastname: Tariq
authors.forename: Saadullah
authors.initials: S
authors.lastname: Khan
authors.forename: Jochen
authors.initials: J
authors.lastname: Hecht
authors.forename: Peter
authors.initials: P
authors.lastname: Krawitz
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003241:Consanguinity; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome; D005260:Female; D005385:Fingers / Q000002:abnormalities; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017689:Polydactyly / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014034:Toes / Q000002:abnormalities
chemical_list: D004268:DNA-Binding Proteins; C581066:zinc finger protein 141, human