J Med Genet 40:473-478 doi:10.1136/jmg.40.7.473
  • Original article

Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide embryopathy

  1. J Kohlhase1,
  2. L Schubert1,
  3. M Liebers1,
  4. A Rauch2,
  5. K Becker3,
  6. S N Mohammed4,
  7. R Newbury-Ecob5,
  8. W Reardon6
  1. 1Institute for Human Genetics, University of Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany
  2. 2Institute of Human Genetics, University Erlangen-Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany
  3. 3Kennedy-Galton Centre, Level 8V, Northwick Park Hospital, Watford Road, Harrow HA1 3UJ, UK
  4. 4Genetics Centre, 8th Floor Guy’s Tower, Guy’s Hospital, St Thomas Street, London SE1 9RT, UK
  5. 5Department of Clinical Genetics, St Michael’s Hospital, Level B, Southwell Street, Bristol BS2 8EG, UK
  6. 6National Centre for Medical Genetics, Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, Ireland
  1. Correspondence to:
 Dr J Kohlhase, Institute for Human Genetics, University of Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany; 
  • Received 19 March 2003
  • Accepted 19 March 2003


We have recently shown that Okihiro syndrome results from mutation in the putative zinc finger transcription factor gene SALL4 on chromosome 20q13.13-13.2. There is considerable overlap of clinical features of Okihiro syndrome with other conditions, most notably Holt-Oram syndrome, a condition in part resulting from mutation of the TBX5 locus, as well as acro-renal-ocular syndrome. We analysed further families/patients with the clinical diagnosis of Holt-Oram syndrome and acro-renal-ocular syndrome for SALL4 mutations. We identified a novel SALL4 mutation in one family where the father was originally thought to have thalidomide embryopathy and had a daughter with a similar phenotype. We also found two novel mutations in two German families originally diagnosed as Holt-Oram syndrome and a further mutation in one out of two families carrying the diagnosis acro-renal-ocular syndrome. Our results show that some cases of “thalidomide embryopathy” might be the result of SALL4 mutations, resulting in an increased risk for similarly affected offspring. Furthermore we confirm the overlap of acro-renal-ocular syndrome with Okihiro syndrome at the molecular level and expand the phenotype of SALL4 mutations.