Abstract
Strabismus refers to an abnormal alignment of the eyes leading to the loss of central binocular vision. Concomitant strabismus occurs when the angle of deviation is constant in all positions of gaze and often manifests in early childhood when it is considered to be a neurodevelopmental disorder of the visual system. As such, it is inherited as a complex genetic trait, affecting 2–4% of the population. A genome-wide association study (GWAS) for self-reported strabismus (1345 cases and 65,349 controls from UK Biobank) revealed a single genome-wide significant locus on chromosome 17q25. Approximately 20 variants across the NPLOC4–TSPAN10–PDE6G gene cluster and in almost perfect linkage disequilibrium (LD) were most strongly associated (lead variant: rs75078292, OR = 1.26, p = 2.24E−08). A recessive model provided a better fit to the data than an additive model. Association with strabismus was independent of refractive error, and the degree of association with strabismus was minimally attenuated after adjustment for amblyopia. The association with strabismus was replicated in an independent cohort of clinician-diagnosed children aged 7 years old (116 cases and 5084 controls; OR = 1.85, p = 0.009). The associated variants included 2 strong candidate causal variants predicted to have functional effects: rs6420484, which substitutes tyrosine for a conserved cysteine (C177Y) in the TSPAN10 gene, and a 4-bp deletion variant, rs397693108, predicted to cause a frameshift in TSPAN10. The population-attributable risk for the locus was approximately 8.4%, indicating an important role in conferring susceptibility to strabismus.
Highlights
Strabismus refers to an abnormal alignment of the eyes leading to loss of binocular vision
There were 72,911 unrelated UK Biobank participants who reported their country of birth as England, Wales or Scotland, whose genetic ancestry principal components clustered with other White British Europeans, and who had responded to the questionnaire item ‘Why were you prescribed glasses/ contact lenses? (You can select more than one answer)’ as well as undergoing an autorefraction assessment
Previous studies have shown that phosphodiesterase 6G (PDE6G) is expressed in both rod and cone photoreceptors (Dvir et al 2010). These results provide strong evidence that a commonly occurring polymorphism situated within a high-linkage disequilibrium (LD) cluster of approximately 20 variants on chromosome 17q25.3 contributes to susceptibility to strabismus
Summary
Strabismus refers to an abnormal alignment of the eyes leading to loss of binocular vision. Concomitant strabismus occurs when the angle of deviation is constant in all positions of gaze and often manifests in early childhood when it is considered to be a neurodevelopmental disorder of the visual system. Concomitant strabismus is most often convergent (‘esotropia’) or divergent (‘exotropia’), vertical misalignment may occur as the primary deviation or in conjunction with esoor exotropia. It is often associated with amblyopia (defined as poor visual acuity in one or both eyes not immediately correctable by glasses and without accompanying ocular pathology) in the deviated eye—either because the squint itself leads to secondary amblyopia in the deviated eye or because reduced vision in one eye compared with the other (e.g. anisometropia, unilateral cataract) secondarily leads to the squint. Strabismus is a feature of several rare syndromes—often in conjunction with intellectual disability—including examples such as Mietens–Weber syndrome and Lamb–Shaffer syndrome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
