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Homozygous stop mutation in AHR causes autosomal recessive foveal hypoplasia and infantile nystagmus.

  • Mayer, Anja K1
  • Mahajnah, Muhammad2, 3
  • Thomas, Mervyn G4
  • Cohen, Yuval3, 5
  • Habib, Adib6
  • Schulze, Martin7
  • Maconachie, Gail D E4
  • AlMoallem, Basamat8, 9
  • De Baere, Elfride8
  • Lorenz, Birgit10
  • Traboulsi, Elias I11
  • Kohl, Susanne1
  • Azem, Abdussalam12
  • Bauer, Peter7
  • Gottlob, Irene4
  • Sharkia, Rajech13, 14
  • Wissinger, Bernd1
  • 1 Molecular Genetics Laboratory, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany. , (Germany)
  • 2 Child Neurology and Development Center, Hillel-Yaffe Medical Center, Hadera, Israel. , (Israel)
  • 3 The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. , (Israel)
  • 4 Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, UK.
  • 5 Ophthalmology Department, Hillel Yaffe Medical Center, Hadera, Israel. , (Israel)
  • 6 Pediatric Department, St. Vincent French Hospital, Nazareth, Israel. , (Israel)
  • 7 Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany. , (Germany)
  • 8 Center for Medical Genetics Ghent, Ghent University and Ghent University Hospital, Ghent, Belgium. , (Belgium)
  • 9 Department of Ophthalmology, King Abdul-Aziz University Hospital, College of Medicine, King Saud University, Riyadh, Saudi Arabia. , (Saudi Arabia)
  • 10 Department of Ophthalmology, Justus Liebig University Giessen, Giessen, Germany. , (Germany)
  • 11 Cole Eye Institute, Cleveland, Ohio, USA.
  • 12 Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, Israel. , (Israel)
  • 13 The Triangle Regional Research and Development Center, Kfar Qari', Israel. , (Israel)
  • 14 Beit-Berl Academic College, Beit-Berl, Israel. , (Israel)
Published Article
Oxford University Press
Publication Date
Jun 01, 2019
DOI: 10.1093/brain/awz098
PMID: 31009037


Herein we present a consanguineous family with three children affected by foveal hypoplasia with infantile nystagmus, following an autosomal recessive mode of inheritance. The patients showed normal electroretinography responses, no signs of albinism, and no anterior segment or brain abnormalities. Upon whole exome sequencing, we identified a homozygous mutation (c.1861C>T;p.Q621*) in the aryl hydrocarbon receptor (AHR) gene that perfectly co-segregated with the disease in the larger family. AHR is a ligand-activated transcription factor that has been intensively studied in xenobiotic-induced toxicity. Further, it has been shown to play a physiological role under normal cellular conditions, such as in immunity, inflammatory response and neurogenesis. Notably, knockout of the Ahr gene in mouse impairs optic nerve myelin sheath formation and results in oculomotor deficits sharing many features with our patients: the eye movement disorder in Ahr-/- mice appears early in development and presents as conjugate horizontal pendular nystagmus. We therefore propose AHR to be a novel disease gene for a new, recessively inherited disorder in humans, characterized by infantile nystagmus and foveal hypoplasia. © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected]

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