Mutations obstructing ATP's emplacement in KIF2A nucleotide-binding pocket causes parenchymal malformations, motor developmental delay, with intellectual disability.

BACKGROUND: KIF2A-related tubulinopathy (MIM: #615411) is a very rare disorder that was clinically characterized as microcephaly, epilepsy, motor developmental disorder (MDD), and various malformations of cortical development, but intellectual disability (ID) or global developmental delay (GDD) was rarely reported in the patients. METHODS: Quad whole-exome sequencing (WES) was performed on the proband, the older brother, and their parents. Sanger sequencing was used to verify the candidate gene variant. RESULTS: The proband, a 23-month-old boy, was previously diagnosed with GDD, and his brother, aged nine years, had ID; both were born to a healthy couple. Quad-WES detected a novel heterozygous KIF2A variant, c.1318G>A (p.G440R), in both the brothers but not in the parents. In-silico analysis revealed that the variants G440R and G318R (which were previously reported in the only reported patient with GDD) lead to markedly enlarged side chains and hinder ATP's emplacement in the NBD pocket. CONCLUSIONS: The type of KIF2A variants that sterically hinder ATP emplacing in KIF2A NBD pocket may be associated with the intellectual disability phenotype; however, further studies are needed. Findings in this case also suggest a rare parental germline mosaicism of KIF2A G440R.

Global analysis of daily new COVID-19 cases reveals many static-phase countries including the United States potentially with unstoppable epidemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is hitting many countries. It is hypothesized the epidemic is differentially progressing in different countries. AIM: To investigate how the COVID-19 epidemic is going on in different countries by analyzing representative countries. METHODS: The status of COVID-19 epidemic in over 60 most affected countries was characterized. The data of daily new cases of each country were collected from Worldometer. The data of daily tests for the United States, Italy, and South Korea were collected from the Website of One World Data. Levels of daily positive COVID-19 tests in the two most affected states of the United States (New York and New Jersey) were collected from the website of the COVID Tracking Project. Statistics were analyzed using Microcal Origin software with ANOVA algorithm, and significance level was set at a P value of 0.05. RESULTS: The COVID-19 epidemic was differentially progressing in different countries. Comparative analyses of daily new cases as of April 19, 2020 revealed that 61 most affected countries can be classified into four types: Downward (22), upward (20), static-phase (12), and uncertain ones (7). In particular, the 12 static-phase countries including the United States were characterized by largely constant numbers of daily new cases in the past over 14 d. Furthermore, these static-phase countries were overall significantly lower in testing density (P = 0.016) but higher in the level of positive COVID-19 tests than downward countries (P = 0.028). These findings suggested that the testing capacity in static-phase countries was lagging behind the spread of the outbreak, i.e., daily new cases (confirmed) were likely less than daily new infections and the remaining undocumented infections were thus still expanding, resulting in unstoppable epidemic. CONCLUSION: Increasing the testing capacity and/or reducing the COVID-19 transmission are urgently needed to stop the potentially unstoppable, severing crisis in static-phase countries.

Validating the accuracy of a model to predict the onset of myopia in children.

PURPOSE: To assess the sensitivity and specificity of models predicting myopia onset among ethnically Chinese children. METHODS: Visual acuity, height, weight, biometry (A-scan, keratometry), and refractive error were assessed at baseline and 3 years later using the same equipment and protocol in primary schools in Xiamen (China) and Singapore. A regression model predicting the onset of myopia < -0.75 diopters (D) after 3 years in either eye among Xiamen children was validated with Singapore data. RESULTS: Baseline data were collected from 236 Xiamen children (mean age, 7.82 ± 0.63 years) and from 1979 predominantly Chinese children in Singapore (7.83 ± 0.84 years). Singapore children were significantly taller and heavier, and had more myopia (31.4% vs. 6.36% < -0.75 D in either eye, P < 0.001) and longer mean axial length. Three-year follow-up was available for 80.0% of Xiamen children and 83.1% in Singapore. For Xiamen, the area under the receiver-operator curve (AUC) in a model including ocular biometry, height, weight, and presenting visual acuity was 0.974 (95% confidence interval [CI], 0.945-0.997). In Singapore, the same model achieved sensitivity, specificity, and positive predictive value of 0.844, 0.650, and 0.669, with an AUC of 0.815 (95% CI, 0.791-0.839). CONCLUSIONS: Accuracy in predicting myopia onset based on simple measurements may be sufficient to make targeted early intervention practical in settings such as Singapore with high myopia prevalence. Models based on cohorts with a greater prevalence of high myopia than that in Xiamen could be used to assess accuracy of models predicting more severe forms of myopia.

[A comparison study of pulsitile ocular blood flow in normal eyes and primary open angle glaucoma].

OBJECTIVE: To compare pulsatile ocular blood flow (POBF) and intraocular pressure (IOP) in primary open angle glaucoma (POAG) and normal control group matched for age, sex and refraction error, to investigate the rule of hem-dynamics in POAG and to determine the sensitivity and specificity of POBF measurement as a diagnostic test for glaucoma. METHODS: Prior to the test a questionnaire was completed to determine age, sex, refractive error, family history of glaucoma, history of eye diseases, ocular medication, medical history and using of systemic beta-blockers. Patients of POAG were determined by following diagnostics standards: (1) Three IOP >25 mm Hg in different times of one day. (2) The fluctuate of IOP > 8 mm Hg during 24 hours. (3) Typical glaucoma changes in the visual field. (4) Typical glaucoma changes in optic disc. There were 100 POAG subjects with single eye observed (50 male and 50 female). We picked up 100 eyes randomly (50 male and 50 female) in 534 normal persons who matched for following conditions: (1) Sex. (2) Discrepancy of age less than 5 years. (3) Discrepancy of the refraction error less than +/- 2.00 DS. as the normal comparison group. The tonometer used was the POBF Tonometry. Pulse amplitude of IOP (PA), pulsatile ocular blood flow (POBF), pulse/heart rate (PR), maximum-IOP (max-IOP), minimum-IOP (min-IOP) and average IOP (aver-IOP) were obtained before the medical therapy and 1 or 2 weeks after the operation. The correlation between the POBF & mean value of the perimeter was analyzed. POBF was analyzed to determine the sensitivity and specificity of POBF measurement as a diagnostic test. RESULTS: The value of POBF in POAG and normal control was (9.72 +/- 3.47) microl/s and (12.04 +/- 4.68) microl/s, respectively. POAG patients' POBF, PV, PA, and AVE-IOP were less than those in the normal control, and the difference was statistically significant. There was no statistically significant correlation between the changes of visual field and POBF (r = 0.224, P = 0.219). The sensitivity and specificity of using the POBF for diagnosis of POAG (less than 10.75 microl/s being abnormal) were 0.422 and 0.623, respectively. CONCLUSION: Abnormal of vas-autoregulation and blood supply play a role in the pathogenesis of POA. Due to the lower sensitivity and specificity, it is not suitable to use POBF as a diagnostic test to distinguish the POAG and normal. But the POBF reflects the change of blood flow in a pulsing cycle and provide more information than the measurement of IOP only.

Near-work activity, night-lights, and myopia in the Singapore-China study.

OBJECTIVE: To investigate the relationship among near-work activity, night-lights, and myopia in schoolchildren in Singapore and Xiamen, China. METHODS: The refractive error and ocular dimensions of 957 Chinese schoolchildren aged 7 to 9 years in Singapore and Xiamen, China, were determined using cycloplegic autorefraction and A-scan ultrasound biometry. Information on near-work activity (number of books read per week, reading in hours per day) and night-light use before age 2 years was obtained. RESULTS: The prevalence rate of myopia was 36.7% (95% confidence interval [CI], 33.0%-40.3%) in Singapore and 18.5% (95% CI, 14.0%-23.1%) in Xiamen, China. The crude odds ratio (OR) of higher myopia (at least -3.0 diopters) for children who read more than 2 books per week was 3.50 (95% CI, 2.15-5.70). In a multivariate logistic regression model, the OR of higher myopia for children who read more was 2.81 (95% CI, 1.69-4.69), adjusted for age, night-light use, parental myopia, and country, whereas there was no association between night-light use before age 2 years and higher myopia (OR, 1.54; 95% CI, 0.92-2.58), after controlling for age, books read per week, parental myopia, and country. MAIN OUTCOME MEASURES: The ORs of higher myopia for children who read more and children who are exposed to night-lights before age 2 years. CONCLUSIONS: Reading (number of books per week) may be associated with higher myopia in Chinese schoolchildren. However, night-light use does not seem to be related to higher myopia.