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Novel mutations in the gene SALL4 provide further evidence for acro-renal-ocular and Okihiro syndromes being allelic entities, and extend the phenotypic spectrum
  1. W Borozdin1,7,
  2. M J Wright2,
  3. R C M Hennekam3,
  4. M C Hannibal4,
  5. Y J Crow5,
  6. T E Neumann6,
  7. J Kohlhase7
  1. 1Institut für Humangenetik, Universität Göttingen, Göttingen, Germany
  2. 2Institute of Human Genetics, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, UK
  3. 3Departments of Pediatrics and Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  4. 4Division of Genetics and Development, Department of Pediatrics, University of Washington, Seattle, WA, USA
  5. 5Department of Clinical Genetics, St James’s University Hospital, Leeds, UK
  6. 6Institut für Humangenetik, Universität Münster, Münster, Germany
  7. 7Institut für Humangenetik und Anthropologie, Universität Freiburg, Freiburg, Germany
  1. Correspondence to:
 Dr J Kohlhase
 Institut für Humangenetik und Anthropologie, Universität Freiburg, Breisacher Str. 33, 79106 Freiburg, Germany;

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The SALL genes, similar to the Drosophila gene spalt,1 encode likely zinc finger transcription factors. In humans, four such genes have been identified to date. Mutations in the gene SALL1 on chromosome 16q12.1 have been associated with Townes-Brocks syndrome and related phenotypes,2,3 and mutations in the gene SALL4 have been shown to be causative in patients with Okihiro syndrome.4,5SALL26 and SALL37 remain to be associated with human disease.

We previously reported frameshift and nonsense mutations in SALL4 in five of eight families segregating the Okihiro syndrome phenotype.5 A further report4 identified two frameshift mutations and one nonsense mutation in three affected kindreds, including the family reported by Okihiro et al.8 In a recent study of patients with a clinical diagnosis of Holt-Oram syndrome, one additional frameshift mutation and an unclear missense change were reported from a family who turned out to have Okihiro syndrome rather than Holt-Oram.9 Furthermore, we reported one previously identified and three novel SALL4 mutations in patients originally diagnosed as having either Holt-Oram syndrome (later revised to Okihiro syndrome based on the observation of a Duane anomaly in at least one of the affected family members in each family), acro-renal-ocular syndrome, or Holt-Oram syndrome versus thalidomide embryopathy.10 While our findings suggested that acro-renal-ocular syndrome and Okihiro syndrome are allelic, evidence so far has come only from one family in which no gross structural eye defects were seen.11 In order to further substantiate our findings we sought to perform mutation analysis in additional patients diagnosed with acro-renal-ocular syndrome, especially those who presented with structural eye defects. We were also interested in extending our studies to further patients with Okihiro syndrome in order to allow a genotype–phenotype correlation. Here we report five novel …

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  • This work was funded by the Wilhelm-Sander-Stiftung (grant 98.075.2 to JK).

  • Conflict of interest: none declared.

  • GenBank accession numbers: SALL4 mRNA, NM_020436; genomic contig NT_011362.