Journal article
Authors list: Mayer, Anja K.; Mahajnah, Muhammad; Thomas, Mervyn G.; Cohen, Yuval; Habib, Adib; Schulze, Martin; Maconachie, Gail D. E.; AlMoallem, Basamat; De Baere, Elfride; Lorenz, Birgit; Traboulsi, Elias, I; Kohl, Susanne; Azem, Abdussalam; Bauer, Peter; Gottlob, Irene; Sharkia, Rajech; Wissinger, Bernd
Publication year: 2019
Pages: 1528-1534
Journal: Brain
Volume number: 142
ISSN: 0006-8950
eISSN: 1460-2156
Open access status: Green
DOI Link: https://doi.org/10.1093/brain/awz098
Publisher: Oxford University Press
Abstract:
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.
Citation Styles
Harvard Citation style: Mayer, A., Mahajnah, M., Thomas, M., Cohen, Y., Habib, A., Schulze, M., et al. (2019) Homozygous stop mutation in AHR causes autosomal recessive foveal hypoplasia and infantile nystagmus, Brain, 142, pp. 1528-1534. https://doi.org/10.1093/brain/awz098
APA Citation style: Mayer, A., Mahajnah, M., Thomas, M., Cohen, Y., Habib, A., Schulze, M., Maconachie, G., AlMoallem, B., De Baere, E., Lorenz, B., Traboulsi, E., Kohl, S., Azem, A., Bauer, P., Gottlob, I., Sharkia, R., & Wissinger, B. (2019). Homozygous stop mutation in AHR causes autosomal recessive foveal hypoplasia and infantile nystagmus. Brain. 142, 1528-1534. https://doi.org/10.1093/brain/awz098
Keywords
AHR; CONGENITAL NYSTAGMUS; consanguinity; foveal hypoplasia; FRMD7; LOCUS; nystagmus; TRANSACTIVATION; VARIANTS
