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

  • Sibel Ugur Iseri
  • Alexander W. Wyatt
  • Gudrun Nürnberg
  • Christian Kluck
  • Peter Nürnberg
  • Graham E. Holder
  • Ed Blair
  • Alison Salt
  • Nicola K. Ragge
Original Investigation


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)


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Sibel Ugur Iseri
    • 1
  • Alexander W. Wyatt
    • 1
  • Gudrun Nürnberg
    • 2
    • 3
    • 4
  • Christian Kluck
    • 2
  • Peter Nürnberg
    • 2
    • 3
    • 4
  • Graham E. Holder
    • 5
  • Ed Blair
    • 6
  • Alison Salt
    • 7
    • 8
  • Nicola K. Ragge
    • 1
    • 9
    • 10
  1. 1.Department of Physiology, Anatomy, and GeneticsUniversity of OxfordOxfordUK
  2. 2.Cologne Center for GenomicsUniversity of CologneCologneGermany
  3. 3.Center for Molecular Medicine CologneUniversity of CologneCologneGermany
  4. 4.Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)University of CologneCologneGermany
  5. 5.Department of ElectrophysiologyMoorfields Eye HospitalLondonUK
  6. 6.Department of Clinical GeneticsOxford Radcliffe HospitalsOxfordUK
  7. 7.Department of PaediatricsMoorfields Eye HospitalLondonUK
  8. 8.Wolfson Neurodisability ServiceGreat Ormond St HospitalLondonUK
  9. 9.Department of Adnexal SurgeryMoorfields Eye HospitalLondonUK
  10. 10.Department of OphthalmologyBirmingham Children’s HospitalBirminghamUK

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