Isolated brachydactyly type E caused by a HOXD13 nonsense mutation: a case report
1 Department of Medical Genetics, University of Medical Sciences in Poznan, Poland, ul. Grunwaldzka 55 paw. 15, 60-352 Poznan, Poland
2 NZOZ Center for Medical Genetics, Poznan, Poland, ul. Grudzieniec 4, 60-601 Poznan, Poland
3 Department of Traumatology, Orthopedics and Hand Surgery, University of Medical Sciences in Poznan, Poland, ul. 28 czerwca 1956 r. 135/147, 61-545 Poznan, Poland
BMC Medical Genetics 2012, 13:4 doi:10.1186/1471-2350-13-4Published: 10 January 2012
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.
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.
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.