title: Isolated brachydactyly type E caused by a HOXD13 nonsense mutation: a case report.
abstract: BACKGROUND
  Brachydactyly type E (BDE; MIM#113300) is characterized by shortening of the metacarpal, metatarsal, and often phalangeal bones, and predominantly affects postaxial ray(s) of the limb. BDE may occur as an isolated trait or as part of a syndrome. Isolated BDE is rare and in the majority of cases the molecular pathogenesis has so far not been resolved. Originally, the molecular cause of isolated BDE has been unravelled in 2 families and shown to result from heterozygous missense mutations in the homeodomain of the HOXD13 gene. Since the initial manuscript, one further HOXD13 mutation has been reported only in a single family manifesting isolated BDE.
  
  
  METHODS
  In this paper, we report on a Polish family exhibiting isolated BDE caused by a novel nonsense heterozygous HOXD13 mutation. We investigated a Polish female proband and her father, both affected by isolated BDE, in whom we identified a nonsense heterozygous mutation c.820C > T(p.R274X) in the HOXD13 gene. So far, only two missense HOXD13 substitutions (p.S308C and p.I314L), localized within the homeodomain of the HOXD13 transcription factor, as well as a single nonsense mutation (p.E181X) were associated with BDE. Both missense changes were supposed to alter DNA binding affinity of the protein.
  
  
  CONCLUSIONS
  The variant p.R274X identified in our proband is the fourth HOXD13 mutation, and the second truncating (nonsense) mutation, reported to result in typical isolated BDE. We refer our clinical and molecular findings to the previously described HOXD13 associated phenotypes and mutations.
authors.affiliation: Department of Medical Genetics, University of Medical Sciences in Poznan, Poland, ul. Grunwaldzka 55 paw. 15, 60-352 Poznan, Poland. jamsheer@wp.pl
authors.forename: Aleksander
authors.initials: A
authors.lastname: Jamsheer
authors.forename: Anna
authors.initials: A
authors.lastname: Sowińska
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.forename: Anna
authors.initials: A
authors.lastname: Latos-Bieleńska
mesh_terms: D000328:Adult; D059327:Brachydactyly / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors