Search

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. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this project was to explore the current standards of clinical care genetic testing and counseling for patients with inherited retinal diseases (IRDs) from the perspective of leading experts in selected European countries. Also, to gather opinions on current bottlenecks and future solutions to improve patient care., Methods: On the initiative of the European Vision Institute, a survey questionnaire with 41 questions was designed and sent to experts in the field from ten European countries. Each participant was asked to answer with reference to the situation in their own country., Results: Sixteen questionnaires were collected by November 2023. IRD genetic tests are performed in clinical care settings for 80% or more of tested patients in 9 countries, and the costs of genetic tests in clinical care are covered by the public health service to the extent of 90% or more in 8 countries. The median proportion of patients who are genetically tested, the median rate of genetically solved patients among those who are tested, and the median proportion of patients receiving counseling are 51-70%, 61-80%, and 61-80%, respectively. Improving the education of healthcare professionals who facilitate patient referrals to specialized centers, improving access of patients to more thorough genotyping, and increasing the number of available counselors were the most advocated solutions., Conclusion: There is a significant proportion of IRD patients who are not genetically tested, whose genetic testing is inconclusive, or who do not receive counseling. Educational programs, greater availability of state-of-the-art genotyping and genetic counselors could improve healthcare for IRD patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)