title: Visual impairment in FOXG1-mutated individuals and mice.
abstract: The Forkead Box G1 (FOXG1 in humans, Foxg1 in mice) gene encodes for a DNA-binding transcription factor, essential for the development of the telencephalon in mammalian forebrain. Mutations in FOXG1 have been reported to be involved in the onset of Rett Syndrome, for which sequence alterations of MECP2 and CDKL5 are known. While visual alterations are not classical hallmarks of Rett syndrome, an increasing body of evidence shows visual impairment in patients and in MeCP2 and CDKL5 animal models. Herein we focused on the functional role of FOXG1 in the visual system of animal models (Foxg1(+/Cre) mice) and of a cohort of subjects carrying FOXG1 mutations or deletions. Visual physiology of Foxg1(+/Cre) mice was assessed by visually evoked potentials, which revealed a significant reduction in response amplitude and visual acuity with respect to wild-type littermates. Morphological investigation showed abnormalities in the organization of excitatory/inhibitory circuits in the visual cortex. No alterations were observed in retinal structure. By examining a cohort of FOXG1-mutated individuals with a panel of neuro-ophthalmological assessments, we found that all of them exhibited visual alterations compatible with high-level visual dysfunctions. In conclusion our data show that Foxg1 haploinsufficiency results in an impairment of mouse and human visual cortical function.
authors.affiliation: CNR Neuroscience Institute, Pisa, Italy.
authors.forename: E M
authors.initials: EM
authors.lastname: Boggio
authors.affiliation: CNR Neuroscience Institute, Pisa, Italy; Scuola Normale Superiore, BioSNS Lab, Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pancrazi
authors.affiliation: CNR Neuroscience Institute, Pisa, Italy; NEUROFARBA Department, University of Firenze, Firenze, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gennaro
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Lo Rizzo
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mari
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Meloni
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ariani
authors.affiliation: CNR Neuroscience Institute, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Panighini
authors.affiliation: CNR Neuroscience Institute, Pisa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Novelli
authors.affiliation: CNR Neuroscience Institute, Pisa, Italy; Tuscan Doctorate School, University of Firenze, Firenze, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Biagioni
authors.affiliation: CNR Neuroscience Institute, Pisa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Strettoi
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, AOUS, Siena, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Hayek
authors.affiliation: Eye Tracking and Visual Application Lab (EVAlab), University of Siena, Siena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rufa
authors.affiliation: CNR Neuroscience Institute, Pisa, Italy; NEUROFARBA Department, University of Firenze, Firenze, Italy. Electronic address: tommaso@in.cnr.it.
authors.forename: T
authors.initials: T
authors.lastname: Pizzorusso
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy. Electronic address: alessandra.renieri@unisi.it.
authors.forename: A
authors.initials: A
authors.lastname: Renieri
authors.affiliation: CNR Neuroscience Institute, Pisa, Italy; Scuola Normale Superiore, BioSNS Lab, Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Costa
mesh_terms: D000818:Animals; D002675:Child, Preschool; D015331:Cohort Studies; D004195:Disease Models, Animal; D005074:Evoked Potentials, Visual / Q000502:physiology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D057895:Haploinsufficiency; D006801:Humans; D007223:Infant; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D012160:Retina / Q000473:pathology / Q000503:physiopathology; D015518:Rett Syndrome / Q000473:pathology / Q000503:physiopathology; D014786:Vision Disorders / Q000235:genetics* / Q000503:physiopathology*; D014792:Visual Acuity / Q000502:physiology; D014793:Visual Cortex / Q000473:pathology / Q000503:physiopathology; D014795:Visual Pathways / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; C489565:Foxg1 protein, mouse; D009419:Nerve Tissue Proteins
keywords: Rett syndrome; autism; cortical blindness; inhibitory interneurons; visual cortex; west syndrome