Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation

Split Hand and Foot Malformation (SHFM) is a birth defect characterized by claw-like appearance of hands and feet.  Several genomic regions have been implicated in the causation of SHFM but SHFM1 is one of the most puzzling among these because despite its frequent involvement in genomic rearrangements, the compelling candidate genes DLX5/DLX6 in that region have never been observed to harbor intragenic mutations.  Shamseldin et al report a family with autosomal recessive SHFM that links to SHFM1 and identify an intragenic mutation in a critical domain in DLX5.  This report not only settles the long debate surrounding SHFM1 by directly implicating DLX5 in the pathogenesis of SHFM but also unravels a previously unrecognized role for this gene in dorso-ventral patterning. (By Dr. Fowzan S Alkuraya, http://jmg.bmj.com/content/early/2011/11/25/jmedgenet-2011-100556.abstract?papetoc )