SUMMARY
Exome sequencing analysis of over 2,000 children with complex malformations of cortical development identified 5 independent homozygous deleterious mutations in KATNB1, encoding the regulatory subunit of the microtubule severing enzyme katanin. Mitotic spindle formation is defective in patient-derived fibroblasts, a consequence of disrupted interactions of mutant KATNB1 with KATNA1, the catalytic subunit of katanin, and other microtubule associated proteins. Loss of KATNB1 orthologs in zebrafish (katnb1) and flies (kat80) results in microcephaly, recapitulating the human phenotype. In the developing Drosophila optic lobe, kat80 loss specifically affects the asymmetrically dividing neuroblasts, which display supernumerary centrosomes and spindle abnormalities during mitosis, leading to cell cycle progression delays and reduced cell numbers. Furthermore, kat80 depletion results in dendritic arborization defects in sensory and motor neurons, affecting neural architecture. Taken together, we provide insight into the mechanisms by which KATNB1 mutations cause human cerebral cortical malformations, demonstrating its fundamental role during brain development.
In the original Figure 5 legend the 3D projections of Z sections and quantifications of glial cells were mislabeled. This has been corrected in the article online.228 Neuron 85, 228, January 7, 2015 ª2015 Elsevier Inc.
Elemental mercury exposure occurs frequently and is potentially a toxic, particularly in children. Children are often attracted to elemental mercury because of its color, density, and tendency to form beads. Clinical manifestations of elemental mercury intoxication vary depending on its form, concentration, route of ingestion, and the duration of exposure. We present data on 179 pediatric cases of elemental mercury poisoning from exposure to mercury in schools in two different provinces of Turkey. Of all patients, 160 children had both touched/played with the mercury and inhaled its vapors, while 26 children had only inhaled the mercury vapor, two children reported having tasted the mercury. The median duration of exposure was 5 min (min 1-max 100), and 11 (6 %) children were exposed to the mercury for more than 24 h at home. More than half of the children (51.9 %) were asymptomatic at admission. Headache was the most common presenting complaint. The results of physical and neurological examinations were normal in 80 (44.6 %) children. Mid-dilated/dilated pupils were the most common neurological abnormality, and this sign was present in 90 (50.2 %) children. Mercury levels were measured in 24-h urine samples daily, and it was shown that the median urinary level of mercury was 29.80 μg/L (min, 2.40 μg/L; max, 4,687 μg/L). A positive correlation was also found between the duration of exposure and urinary mercury levels (r = 0.23, p = 0.001). All patients were followed up for 6 months. On the first follow-up visit performed 1 month after discharge, the neurological examinations of all patients were normal except for those patients with peripheral neuropathy and visual field defects. On the last follow-up visit at the sixth month, only two children still experienced visual field defects. In conclusion, this study is one of the largest case series of mercury intoxication of students in schools. Elemental mercury exposure can be potentially toxic, and its symptomatology is variable, particularly in children. Therefore, school staff and children should be aware of the risk of mercury toxicity. Pediatricians also need to warn parents and children about the hazards of playing with any chemical.
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