GABAA receptor subunit gene (GABR) mutations are significant causes of epilepsy, including syndromic epilepsy. This report for the first time, describes intractable epilepsy and blindness due to optic atrophy in our patient, who has a microdeletion of the GABRA1 and GABRG2 genes. We then characterized the molecular phenotypes and determined patho-mechanisms underlying the genotype-phenotype correlations in a mouse model who is haploinsufficient for both genes (Gabra1+/-/Gabrg2+/- mouse).
Electroencephalography was conducted in both human and mice with the same gene loss. GABAA receptor expression was evaluated by biochemical and imaging approaches. Optic nerve atrophy was evaluated with fundus photography in human while electronic microscopy, visual evoked potential and electroretinography recordings were conducted in mice.
The patient has bilateral optical nerve atrophy. Mice displayed spontaneous seizures, reduced electroretinography oscillatory potential and reduced GABAA receptor α1, β2 and γ2 subunit expression in various brain regions. Electronic microscopy showed that mice also had optic nerve degeneration, as indicated by increased G-ratio, the ratio of the inner axonal diameter to the total outer diameter, suggesting impaired myelination of axons. More importantly, we identified that phenobarbital was the most effective anticonvulsant in mice and the patient\'s seizures were also controlled with phenobarbital after failing multiple anti-seizure drugs.
This study is the first report of haploinsufficiency of two GABR epilepsy genes and visual impairment due to altered axonal myelination and resultant optic nerve atrophy. The study suggests the far-reaching impact of GABR mutations and the translational significance of animal models with the same etiology.

OBJECTIVE: To investigate the pathogenic gene in a child with optic atrophy and analyze the influence of this gene mutation on protein structure.
OBJECTIVE: We collected the clinical record of the 13-year-old girl and her relatives. The child received examinations of the visual acuity, visual field, fundus, OCT, visual-evoked potential (VEP) and the nerve system, underwent brain MRI and was followed up for 1 year. Genomic DNA was extracted from the peripheral blood of the child and her parents for next-generation sequencing of the whole exon. The pathogenic gene mutation was identified and the resultant changes in the protein structure was analyzed.
OBJECTIVE: The patient presented with impaired vision and optic nerve atrophy in both eyes with low amplitude of VEP, but did not show dystonia or pyramidal tract symptom. Brain MRI detected no leukodystrophy. Genetic analysis suggested a heterozygous c.53_54delTG mutation in exon 1 in the NDUFV1 gene of complex I, which caused a frameshift starting with the codon valine 18, thus changing the amino acid to an Alanine residue and creating a premature stop codon at position 20 of the new reading frame (p.Val18AlafsX20). A heterozygous for c.1162+4A>C: IVS8 + 4A>C in intron 8 was also found. Protein structure analysis showed the missing of important structure of NDUFV1 subunit in complex I.
OBJECTIVE: We identified a novel NDUFV1 mutation in a child with optic nerve atrophy. This finding may provide further insight into the genotype-phenotype correlations for NDUFV1 gene.

Pathological optic disc cupping (ODC) is predominantly referred to as glaucoma; however, it is not only glaucoma that leads to pathological optic disc excavation. A number of other nonglaucomatous diseases also result in optic atrophy and excavation of the optic disc. Therefore, in the present study, the etiology of nonglaucomatous optic disc cupping (NGODC) was analyzed and differentiated from glaucomatous optic disc cupping (GODC). The morphology and clinical data of 19 eyes, from 12 patients exhibiting NGODC, were analyzed. Of the 12 cases, none were diagnosed with glaucoma, four presented with optic neuritis, one with Devic\'s disease, one with Leber\'s hereditary optic neuropathy, two with pituitary adenoma, one with basal ganglia cerebral hemorrhage, one with cilioretinal artery occlusion associated with central retinal vein occlusion, one with central retinal artery occlusion and the remaining patient exhibited optic nerve injuries. The key features that differentiated NGODC from GODC were the color of the optic disc rim and the correlation between visual field defects and the disc appearance. The focally notched disc also aided in distinguishing between the two disorders. The results of the present study indicated that it is critical to acknowledge that nonglaucomatous diseases also lead to ODC and that distinguishing between them is necessary.