Abstract
BackgroundFemale-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.ResultsWe 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.ConclusionsThis is the first description of a Caucasian family displaying Myopia-26. We present two hypotheses that could potentially explain the pathomechanism of this disease.
Highlights
Female-limited early-onset high myopia, 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
In our study we investigated a large family of five generations displaying female-limited early onset high myopia (eoHM)
Recording the personal and familial medical histories of the patients allowed the compilation of their pedigree (Fig. 1)
Summary
Female-limited early-onset high myopia, 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. This disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesis. One of the most curious and exceptional modes of transmission is that seen for Myopia-26, displaying X-linked dominant inheritance. This rare disease, described earlier only in three Asian families paradoxically affects females only, with male hemizygotes being asymptomatic (emmetropic) carriers [6]. Associated symptoms were not reported for those cases, neither was a potential mechanism of pathogenesis provided
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