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J Med Genet 49:16-20 doi:10.1136/jmedgenet-2011-100556
  • New loci
  • Original article

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

  1. Fowzan S Alkuraya1,3,4
  1. 1Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  2. 2Children's Hospital, King Saud Medical City, Riyadh, Saudi Arabia
  3. 3Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia
  4. 4Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
  1. Correspondence to Dr Fowzan S Alkuraya, Developmental Genetics Unit, King Faisal Specialist Hospital and Research Center, MBC-03 PO BOX 3354, Riyad 11211, Saudi Arabia; falkuraya{at}kfshrc.edu.sa
  1. Contributors Hanan Shamseldin generated and analysed data and edited the manuscript; Maha A Faden generated and analysed data and wrote the manuscript; Walid Alashram generated and analysed data; Fowzan S Alkuraya supervised, generated and analysed data and wrote the manuscript.

  • Received 6 October 2011
  • Revised 2 November 2011
  • Accepted 3 November 2011
  • Published Online First 25 November 2011

Abstract

Background Split hand and foot malformation (SHFM) refers to a genetically heterogeneous developmental disorder of the hands and feet that presents as median ray deficiency of varying severity. 7q21.3 (SHFM1) is one of six loci described to date, and although DLX5 and DLX6 are compelling candidates in that locus, no intragenic mutations have been described in either of these genes.

Methods The authors combined autozygome analysis and exome sequencing to study a consanguineous family with a highly unusual SHFM phenotype, where there is associated dorsalisation of the hands.

Results A novel missense mutation in a highly conserved residue of the homeobox domain of DLX5 was identified. Unlike previously reported position effect mutations in SHFM1, this first documented intragenic DLX5 mutation is also accompanied by abnormal dorsal-ventral patterning.

Conclusion This study identified the first intragenic DLX5 mutation in SHFM and raises interesting possibilities about a dual role for DLX5 in limb development.

Footnotes

  • Funding This study was supported by KACST, grant number 09-MED941-20 and Dubai-Harvard Foundation for Medical Research Collaborative Grant.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by IRB at King Faisal Specialist Hospital and Research Center.

  • Provenance and peer review Not commissioned; externally peer reviewed.