A HS6ST2 gene variant associated with X-linked intellectual disability and severe myopia in two male twins

X-linked intellectual disability (XLID) refers to a clinically and genetically heterogeneous neurodevelopmental disorder, in which males are more heavily affected than females. Among the syndromic forms of XLID, identified by additional clinical signs as part of the disease spectrum, the association between XLID and severe myopia has been poorly characterized. We used whole exome sequencing (WES) to study two Italian male twins presenting impaired intellectual function and adaptive behavior, in association with severe myopia and mild facial dysmorphisms. WES analysis detected the novel, maternally inherited, mutation c.916G > C (G306R) in the X-linked heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) gene. HS6ST2 transfers sulfate from adenosine 3′-phosphate, 5′-phosphosulfate to the sixth position of the N-sulphoglucosamine residue in heparan sulfate (HS) proteoglycans. Low HS sulfation levels are associated with defective optic disc and stalk morphogenesis during mammalian visual system development. The c.916G>C variant affects the HS6ST2 substrate binding site, and its effect was considered “deleterious” by in-silico tools. An in-vitro enzymatic assay showed that the HS6ST2 mutant isoform had significantly reduced sulphotransferase activity. Taken together, the results suggest that mutant HS6ST2 is possibly involved in the development of myopia and cognitive impairment, characteristics of the probands reported here.     

ENABLE (Exportable Notation and Bookmark List Engine): an Interface to Manage Tumor Measurement Data from PACS to Cancer Databases

Journal of Digital Imaging - Oncologists evaluate therapeutic response in cancer trials based on tumor quantification following selected “target” lesions over time. At our cancer...     

The Prevalence of Strabismus,Heterophorias, and Their Associated Factors in Underserved Rural Areas of Iran

Purpose: To determine the prevalence of different types of strabismus and heterophoria and their associated factors in underserved rural areas of Iran. Methods: Two rural areas in the north and southwest of Iran were randomly sampled using multistage cluster sampling. Individuals aged over 1 year, totaling 3851, were invited to participate in the study. In addition to collecting demographic data, optometric examinations were performed for each participant. Unilateral and alternating cover tests were performed at far (6 m) and near (40 cm) to detect tropia and phoria, respectively, and the magnitude of the deviation was measured using alternating cover test and prism bar. Tropia was defined as the presence of constant unilateral or alternating horizontal strabismus (exotropia or esotropia) at either far or near fixation distances. Far and near exophoria were defined as more than 3 prism diopters (PD) and 9 PD of exophoria at far and near fixation distances, respectively. Far esophoria was defined as more than 1 PD of esophoria at far. Near esophoria was defined as any amount of esophoria at near. Results: Of 3851 selected individuals, 3314 (86.5%) participated in the study. After excluding those who met the exclusion criteria or had missing data, eventually there were 3248 subjects available for this analysis. The prevalence of tropia and phoria was 4.3% (95% CI: 3.28-5.33) and 28.37% (95% CI: 19.12 -37.61), respectively. The prevalence of exotropia and esotropia was 3.87% (95% CI: 2.77-4.98) and 0.43% (95% CI: 0.19-0.67), respectively. The prevalence of near exophoria, far exophoria, near esophoria, and far esophoria was 25.96 (95% CI: 16.71-35.2), 4.82% (95% CI: 0.23-9.41), 0.47% (95% CI: 0.2-0.75), and 0.34% (95% CI: 0.06-0.63), respectively. In this study, the prevalence of tropia had no significant association with age, sex, living place, and refractive errors (all P values >0.05), while the prevalence of phoria increased significantly with increasing age (P<0.001) and was also significantly associated with living place (P<0.001). Conclusion: The prevalence of tropia and phoria was high in our study. Moreover, the prevalence of exotropia and exophoria was higher than esotropia and esophoria. The prevalence of phoria was significantly higher in older age groups and in the participants living in the southern villages.