Human Genetics

, Volume 119, Issue 1, pp 154–161

A SALL4 zinc finger missense mutation predicted to result in increased DNA binding affinity is associated with cranial midline defects and mild features of Okihiro syndrome

Authors

  • Jan Miertus
    • International Centre for Genetic Engineering and Biotechnology
    • Medical Genetics Department, Academic hospital San Giovanni Battista di TorinoUniversity of Torino
  • Wiktor Borozdin
    • Institut für Humangenetik und AnthropologieUniversität Freiburg
  • Vladimir Frecer
    • International Centre for Science and High TechnologyUNIDO, AREA Science Park
    • Cancer Research Institute, Slovak Academy of Sciences
  • Giorgio Tonini
    • Endocrinology Unit, I.R.C.C.S. “Burlo Garofolo”
  • Sara Bertok
    • Medical Genetics Service and Department of Medical GeneticsUniversity of Trieste, I.R.C.C.S. “Burlo Garofolo”
  • Antonio Amoroso
    • Medical Genetics Service and Department of Medical GeneticsUniversity of Trieste, I.R.C.C.S. “Burlo Garofolo”
    • Department of Genetics, Biology, and BiochemistryUniversity of Torino
  • Stanislav Miertus
    • International Centre for Science and High TechnologyUNIDO, AREA Science Park
    • Institut für Humangenetik und AnthropologieUniversität Freiburg
Original Investigation

DOI: 10.1007/s00439-005-0124-7

Cite this article as:
Miertus, J., Borozdin, W., Frecer, V. et al. Hum Genet (2006) 119: 154. doi:10.1007/s00439-005-0124-7

Abstract

Truncating mutations of the gene SALL4 on chromosome 20q13.13–13.2 cause Okihiro and acro-renal-ocular syndromes. Pathogenic missense mutations within the SALL4 or SALL1 genes have not yet been reported, raising the question which phenotypic features would be associated with them. Here we describe the first missense mutation within the SALL4 gene. The mutation results in an exchange of a highly conserved zinc-coordinating Histidine crucial for zinc finger (ZF) structure within a C2H2 double ZF domain to an Arginine. Molecular modeling predicts that this exchange does not result in a loss of zinc ion binding but leads to an increased DNA-binding affinity of the domain. The index patient shows mild features of Okihiro syndrome, but in addition cranial midline defects (pituitary hypoplasia and single central incisor). This finding illustrates that the phenotypic and functional effects of SALL4 missense mutations are difficult to predict, and that other SALL4 missense mutations might lead to phenotypes not overlapping with Okihiro syndrome.

Copyright information

© Springer-Verlag 2005