Non\u2011syndromic isolated dominant optic atrophy caused by the p.R468C mutation in the AFG3 like matrix AAA peptidase subunit 2 gene

Autosomal dominant optic atrophy (DOA) is the most frequent form of hereditary optic atrophy, a disease presenting with considerable inter- and intra-familial clinical variability. Although a number of mutations in different genes are now known to cause DOA, many cases remain undiagnosed. In an attempt to identify the underlying genetic defect, whole exome sequencing was performed in a 19-year-old male that had been affected by isolated DOA since childhood. The exome sequencing revealed a pathogenic mutation (p.R468C, c.1402C>T) in the AFG3 like matrix AAA peptidase subunit 2 (AFG3L2) gene, a gene known to be associated with spinocerebellar ataxia. The patient did not show any signs other than DOA. Thus, the result demonstrates the possibility that mutations in the AFG3L2 gene may be a cause of isolated autosomal DOA

Illusory Contours over Pathological Retinal Scotomas

Our visual percepts are not fully determined by physical stimulus inputs. Thus, in visual illusions such as the Kanizsa figure, inducers presented at the corners allow one to perceive the bounding contours of the figure in the absence of luminance-defined borders. We examined the discrimination of the curvature of these illusory contours that pass across retinal scotomas caused by macular degeneration. In contrast with previous studies with normal-sighted subjects that showed no perception of these illusory contours in the region of physiological scotomas at the optic nerve head, we demonstrated perfect discrimination of the curvature of the illusory contours over the pathological retinal scotoma. The illusion occurred despite the large scar around the macular lesion, strongly reducing discrimination of whether the inducer openings were acute or obtuse and suggesting that the coarse information in the inducers (low spatial frequency) sufficed. The result that subjective contours can pass through the pathological retinal scotoma suggests that the visual cortex, despite the loss of bottom-up input, can use low-spatial frequency information from the inducers to form a neural representation of new complex geometrical shapes inside the scotoma

Non-syndromic isolated dominant optic atrophy caused by the p.R468C mutation in the AFG3L2 gene

Background: Autosomal Dominant Optic Atrophy (DOA) is the most frequent form of hereditary optic atrophy, a disease presenting with considerable inter- and intra-familial clinical variability. Although a number of mutations in different genes are now known to cause DOA, many cases remain undiagnosed. Methods: In attempt to identify the underlying genetic defect, whole exome sequencing was performed in a 19 years old male affected by isolated DOA since childhood. Results: Exome sequencing revealed a pathogenic mutation (p.R468C, c.1402C>T) in the AFG3L2 gene, a gene known to be associated with spinocerebellar ataxia. Our patient does not show any signs other than DOA. Conclusions: Our result raises the possibility that mutations in the AFG3L2 gene may be a cause of isolated autosomal dominant optic atrophy

Patients' characteristics.

<p>Patients' characteristics.</p

Discrimination of four inducers angle.

<p>Psychometric functions are fit to the probability of discriminating whether the openings of the four inducers simultaneously presented were acute or obtuse, as a function of the deviation of openings' angles from 90 deg and plotted separately for each JMD subject and his or her two age-matched controls.</p

Stimuli.

<p>To perceive the illusory gray rectangle in the absence of luminance edges defining its control, the openings of the four white inducers must be specular (left) and form the corners of the illusory rectangle. The figure shows an example of a thin Kanizsa illusory rectangle formed by inducer openings with acute angles. Only the global grouping of the four inducers creates the illusion. As a matter of fact, when the same four inducers are all oriented in the same direction, the illusory shape is not perceived (right).</p

Discrimination of one inducer angle.

<p>Psychometric functions are fit to the probability of discriminating whether the opening of one of the four inducers randomly presented was acute or obtuse as a function of the deviation of openings' angles from 90 deg and plotted separately for each JMD subject and his or her two age-matched controls.</p

Contrast sensitivity curve.

<p>Contrast sensitivity curves of the right and left eyes are measured for spatial frequencies ranging between 0.5 to 60 cycles × degree (cpd). The curves of each JMD participant (filled symbols) are compared with the average contrast sensitivity of the six controls (empty symbols). Error bars indicate SD for the control data.</p