Identification of de novo Mutations in the Chinese Autism Spectrum Disorder Cohort via Whole-Exome Sequencing Unveils Brain Regions Implicated in Autism / 神经科学通报·英文版

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.

The expressions of aerobic glycolytic enzymes in the cerebellums of patients with autism / 中国神经精神疾病杂志

Objective To study the expression levels of aerobic glycolytic enzymes in the cerebellums and its correlation with pathogenesis of autism in patients with autism. Methods The Western blotting was used to quantita-tively examine the expression levels of aerobic glycolytic enzymes, including HK-Ⅰ, HK-Ⅱ, PFKP, PKM1/2, PKM2, GAPDH, PDH and LDHA in the cerebellums of eight patients with autism and eight age-matched controls. Results Compared to controls, PDH expression was significantly decreased [(0.715±0.342) vs.(1.028±0.203), P=0.043], while expression of other seven aerobic glycolytic enzymes remained unchanged ( P>0 . 05 ) in the cerebellums of patients with autism. Conclusion The present study has revealed a decrease in the expression of PDH in the cerebellums of patients with autism, which may be involved in the pathologic process of autism.

Determination of Indigo and Indirubin in Baphicacanthus cusia from Different Producing Areas and Medicinal Parts by RP-HPLC / 医药导报

Objective To establish a RP-HPLC method for determining indigo and indirubin in Baphicacanthus cusia from different producing areas and medicinal parts. Methods The separation was achieved by an Agilent TC-C18 Column (4.6 mm×250 mm, 5 μm) at 25 ℃ using methanol-water (75??25) as mobile phase at a flow rate of 1 mL??min-1.The detection wavelength was 290 nm. Results Indigo had a good linear relationship with peak area at range of 0. 051 3-0.820 8 μg (r=0.999 3).The recovery rate was 99.00% and RSD was 1.30% (n=6).Indirubin had a good linear relationship with peak area at range of 0.049 5-0.792 0 μg (r=0.999 9).The recovery rate was 98.88% and RSD was 1.51% (n=6). Conclusion The contents of the two components are obviously different in Baphicacanthus cusia because of different places or medicinal parts. The proposed method is simple, rapid and reliable. This method for determination of indigo and indirubin in Baphicacanthus cusia by RP-HPLC provides a basis for quality control of Baphicacanthus cusia.