ISCEV extended protocol for the S-cone ERG

et al. 2021

Orphanet J Rare Dis

Background Female-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesis. Results We found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- testing) as well as colour vision- and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. Ophthalmological examinations did not reveal any signs of cone dystrophy as opposed to animal models. Electrophysiology and colour vision tests similarly did not evidence a general cone system alteration, rather a central macular dysfunction affecting both the inner and outer (postreceptoral and receptoral) retinal structures in all patients with ARR3 mutation. Conclusions This is the first description of a Caucasian family displaying Myopia-26. We present two hypotheses that could potentially explain the pathomechanism of this disease.

Section: Discussionmentioning

confidence: 99%

Myopia-26, the female-limited form of early-onset high myopia, occurring in a European family

et al. 2021

Orphanet J Rare Dis

“…From the clinical point of view, our next investigative steps seem well de ned: i) cone-speci c ERGs (Scone ERGs and ON/OFF ERGs) to isolate individual (L, M, or S) cone responses (41) and thus support or exclude our selective cone dysfunction hypothesis; ii) post-illumination pupil response (PIPR) to test melanopsin expressing ipRGC function (21) and thus shed light on the extent of ipRGC damage. iii) longterm follow-up of the progression of a potential POAG monitoring IOPs, visual eld defects, optic nerve head appearances and RNFL OCTs.…”

Section: Discussionmentioning

confidence: 99%

Myopia-26, the female-limited form of early-onset high myopia, occurring in a European family

et al. 2020

Preprint

Background: Female-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesisResults: We found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- testing) as well as colour vision- and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. Ophthalmological examinations did not reveal any signs of cone dystrophy as opposed to animal models. Electrophysiology and colour vision tests similarly did not evidence a general cone system alteration, rather a central macular dysfunction affecting both the inner and outer (postreceptoral and receptoral) retinal structures in all patients with ARR3 mutation. Conclusions: This is the first description of a Caucasian family displaying Myopia-26. We present two hypotheses that could potentially explain the pathomechanism of this disease.

“…From the clinical point of view, our next investigative steps seem well defined: i) cone-specific ERGs using the "silent substitution" paradigm [43] to isolate individual (L, M, or S) cone responses [44] and thus support or exclude our selective cone dysfunction hypothesis; ii) post-illumination pupil response (PIPR) to test melanopsin expressing ipRGC function [21] and thus shed light on the extent of ipRGC damage. iii) long-term follow-up of POAG progression monitoring IOPs and visual field defects.…”

Section: Discussionmentioning

confidence: 99%

Myopia-26, the female-limited form of early-onset high myopia is associated with retinal ganglion cell dysfunction and primary open angle glaucoma

et al. 2020

Preprint

Background: Female-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesis Results: We found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- and colour vision testing) and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. We found variously impaired visual fields in four affected myopic females and a carrier male. Abnormal pattern electroretinography responses were detected in both symptomatic and carrier patients. Conclusions: This is the first description of a Caucasian family displaying Myopia-26. Pattern electroretinography implies retinal ganglion cell dysfunction present in both sexes. In conjunction with the visual field loss, this suggests the development of age-related open angle glaucoma in addition to high myopia, both attributable to the rare genetic variant of ARR3. We present two hypotheses that could potentially explain the pathomechanism of this disease.