Human Genetics

, Volume 128, Issue 1, pp 51–60

Use of genome-wide SNP homozygosity mapping in small pedigrees to identify new mutations in VSX2 causing recessive microphthalmia and a semidominant inner retinal dystrophy

Authors

  • Sibel Ugur Iseri
    • Department of Physiology, Anatomy, and GeneticsUniversity of Oxford
  • Alexander W. Wyatt
    • Department of Physiology, Anatomy, and GeneticsUniversity of Oxford
  • Gudrun Nürnberg
    • Cologne Center for GenomicsUniversity of Cologne
    • Center for Molecular Medicine CologneUniversity of Cologne
    • Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)University of Cologne
  • Christian Kluck
    • Cologne Center for GenomicsUniversity of Cologne
  • Peter Nürnberg
    • Cologne Center for GenomicsUniversity of Cologne
    • Center for Molecular Medicine CologneUniversity of Cologne
    • Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)University of Cologne
  • Graham E. Holder
    • Department of ElectrophysiologyMoorfields Eye Hospital
  • Ed Blair
    • Department of Clinical GeneticsOxford Radcliffe Hospitals
  • Alison Salt
    • Department of PaediatricsMoorfields Eye Hospital
    • Wolfson Neurodisability ServiceGreat Ormond St Hospital
    • Department of Physiology, Anatomy, and GeneticsUniversity of Oxford
    • Department of Adnexal SurgeryMoorfields Eye Hospital
    • Department of OphthalmologyBirmingham Children’s Hospital
Original Investigation

DOI: 10.1007/s00439-010-0823-6

Cite this article as:
Iseri, S.U., Wyatt, A.W., Nürnberg, G. et al. Hum Genet (2010) 128: 51. doi:10.1007/s00439-010-0823-6

Abstract

Mutations in the visual system homeobox 2 gene (VSX2, also known as CHX10), which encodes a retinal transcription factor from the paired homeobox family, have been implicated in recessive isolated microphthalmia. In this study, we use genome-wide single nucleotide polymorphism homozygosity mapping in unrelated small consanguineous pedigrees and a candidate gene approach to identify three further causative VSX2 mutations (two novel and one previously reported). All affected individuals with homozygous mutations had bilateral anophthalmia or severe microphthalmia with absent vision. In addition, we identified a novel inner retinal dystrophy in two carrier parents suggesting a semidominant effect for this particular VSX2 mutation. A further study of individuals with retinal degenerative conditions may reveal a causative role for heterozygous mutations in VSX2.

Supplementary material

439_2010_823_MOESM1_ESM.doc (175 kb)
Supplementary material (DOC 175 kb)

Copyright information

© Springer-Verlag 2010