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

  • Jan Miertus
  • Wiktor Borozdin
  • Vladimir Frecer
  • Giorgio Tonini
  • Sara Bertok
  • Antonio Amoroso
  • Stanislav Miertus
  • Jürgen Kohlhase
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

Authors and Affiliations

  • Jan Miertus
    • 2
    • 7
  • Wiktor Borozdin
    • 3
  • Vladimir Frecer
    • 4
    • 5
  • Giorgio Tonini
    • 6
  • Sara Bertok
    • 1
  • Antonio Amoroso
    • 1
    • 8
  • Stanislav Miertus
    • 4
  • Jürgen Kohlhase
    • 3
  1. 1.Medical Genetics Service and Department of Medical GeneticsUniversity of Trieste, I.R.C.C.S. “Burlo Garofolo”TriesteItaly
  2. 2.International Centre for Genetic Engineering and BiotechnologyTriesteItaly
  3. 3.Institut für Humangenetik und AnthropologieUniversität FreiburgFreiburgGermany
  4. 4.International Centre for Science and High TechnologyUNIDO, AREA Science ParkTriesteItaly
  5. 5.Cancer Research Institute, Slovak Academy of SciencesBratislavaSlovakia
  6. 6.Endocrinology Unit, I.R.C.C.S. “Burlo Garofolo”TriesteItaly
  7. 7.Medical Genetics Department, Academic hospital San Giovanni Battista di TorinoUniversity of TorinoTorinoItaly
  8. 8.Department of Genetics, Biology, and BiochemistryUniversity of TorinoTorinoItaly