Visual impairment in FOXG1-mutated individuals and mice

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• The Forkhead Box G1 (FOXG1) gene is crucial for mammalian forebrain development.
• Mutations in FOXG1 are linked to Rett Syndrome, and visual impairments are increasingly noted in affected individuals and animal models.

Purpose of the Study:

• To investigate the functional role of FOXG1 in the visual system of animal models and human subjects with FOXG1 mutations.
• To determine if FOXG1 haploinsufficiency affects visual cortical function.

Main Methods:

• Assessed visual physiology in Foxg1(+/Cre) mice using visually evoked potentials.
• Performed morphological investigation of visual cortex circuits in mice.
• Conducted neuro-ophthalmological assessments in a cohort of individuals with FOXG1 mutations.

Main Results:

• Foxg1(+/Cre) mice showed reduced visually evoked potential amplitude and visual acuity.
• Abnormalities in excitatory/inhibitory circuit organization were found in the visual cortex of mice, without retinal changes.
• All examined FOXG1-mutated individuals exhibited visual alterations indicative of high-level visual dysfunctions.

Conclusions:

• Foxg1 haploinsufficiency leads to impaired visual cortical function in mice.
• The findings demonstrate that FOXG1 mutations cause visual cortical dysfunction in humans.