Homozygous stop mutation in AHR causes autosomal recessive foveal hypoplasia and infantile nystagmus.
Brain
; 142(6): 1528-1534, 2019 06 01.
Article
in En
| MEDLINE
| ID: mdl-31009037
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Aryl Hydrocarbon
/
Nystagmus, Congenital
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Basic Helix-Loop-Helix Transcription Factors
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Optic Nerve Hypoplasia
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Homozygote
Type of study:
Diagnostic_studies
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Etiology_studies
/
Prognostic_studies
Limits:
Animals
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Child
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Female
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Humans
/
Male
Language:
En
Journal:
Brain
Year:
2019
Document type:
Article
Affiliation country:
Germany