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

Anja K. Mayer, Muhammad Mahajnah, Mervyn G. Thomas, Yuval Cohen, Adib Habib, Martin Schulze, Gail D.E. MacOnachie, Basamat Almoallem, Elfride De Baere, Birgit Lorenz, Elias I. Traboulsi, Susanne Kohl, Abdussalam Azem, Peter Bauer, Irene Gottlob, Rajech Sharkia, Bernd Wissinger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish
Pages (from-to)1528-1534
Number of pages7
Issue number6
StatePublished - 1 Jun 2019


FundersFunder number
Ghent University Special Research Fund
Hertie Institute for Clinical Brain Research
National Institute for Health and Care Research2980
Deutsche ForschungsgemeinschaftWI 1189/8-1, SCHO 754/5–2
Eberhard Karls Universität Tübingen5009/2010
Fonds Wetenschappelijk Onderzoek
Universiteit GentBOF15/GOA/ 011


    • AHR
    • consanguinity
    • foveal hypoplasia
    • nystagmus


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