Proximal spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder caused by deletion or mutation of the survival of motor neuron 1 (SMN1). Here, we studied SMA molecular pathology in 653 Chinese patients and found approximately 88.2% with homozygous SMN1 exon 7 deletion and 6.3% with heterozygous exon 7 loss using multiplex ligation-dependent probe amplification. SMN1 variants were detected in 34 patients with heterozygous SMN1 loss by clone sequencing. In 27 of them, 15 variants were identified: five were unreported novel variants [c.-7_9del(p.0), p.Tyr109Cys, p.Ile249Tyrfs*16, p.Tyr272Trpfs*35, and c.835-5T>G], five were previously found only in Chinese patients (p.Ser8Lysfs*23, p.Gln14*, p.Val19Glyfs*21, p.Leu228*, and p.Tyr277Cys), and five were reported in other populations [p.Ala2Gly, p.Gln15*, p.Glu134Lys, p.Ser230Leu, and c.863G>T (r.835_*3del, p.Gly279Glufs*5)]. Variants p.Ser8Lysfs*23 and p.Leu228* were the most common in Chinese SMA. Five variants (p.Ser8Lysfs*23, p.Gln14*, p.Gln15*, p.Val19Glyfs*21, and p.Leu228*) resulted in premature stop codons, likely causing SMN1 mRNA nonsense-mediated decay. The novel variant c.-7_9del (p.0) caused deletion of the translation start codon (AUG), resulting in full-length SMN protein loss. The novel variant c.835-5T>G, located in a splice site, resulted in 90% exon 7 skipping. Our study could facilitate early diagnosis for SMA patients in mutation detection and revealed the specific mutation spectrum of SMN1 in Chinese SMA and high genetic heterogeneity in subtle variants observed between patients from China and Caucasians.

Understanding how the mappings between orthography and phonology in alphabetic languages are learned, represented and processed has been enhanced by the cognitive neuropsychological investigation of patients with acquired reading and writing disorders. During the past decade, this methodology has been extended to understanding reading and writing in Chinese leading to new insights about language processing, dyslexia and dysgraphia. The aim of this paper is to review reports of patients who have acquired dyslexia and acquired dysgraphia in Chinese and describe the functional architecture of the reading and writing system. Our conclusion is that the unique features of Chinese script will determine the symptoms of acquired dyslexia and dysgraphia in Chinese.

Abstract:The homozygous loss of the survival motor neuron 1 (SMN1) gene is the primary cause of spinal muscular atrophy (SMA), a neuromuscular degenerative disease. A genetically similar gene, SMN2, which is not functionally equivalent in all SMA patients, modifies the clinical SMA phenotypes. We analyzed the methylation levels of 4 CpG islands (CGIs) in SMN2 in 35 Chinese children with SMA by MassARRAY. We found that three CpG units located in CGI 1 (nucleotides (nt) −871, −735) and CGI 4 (nt +999) are significantly hypomethylated in SMA type III compared with type I or II children after receiving Bonferroni correction. In addition to the differentially methylated CpG unit of nt −871, the methylation level of the nt −290/−288/−285 unit was negatively correlated with the expression of SMN2 full-length transcripts (SMN2-fl). In addition, the methylation level at nt +938 was inversely proportional to the ratio of SMN2-fl and lacking exon 7 transcripts (SMN2-7, fl/7), and was not associated with the SMN2 transcript levels. Thus, we can conclude that SMN2 methylation may regulate the SMA disease phenotype by modulating its transcription.

NMDA receptor (NMDAR) antagonists such as ketamine, can reproduce many of the symptoms of schizophrenia. A reliable indicator of NMDAR channel blocker action in vivo is the augmentation of neuronal oscillation power. Since the coordinated and rhythmic activation of neuronal assemblies (oscillations) is necessary for perception, cognition and working memory, their disruption (inappropriate augmentation or inhibition of oscillatory power or inter-regional coherence) both in psychiatric conditions and with NMDAR antagonists may reflect the underlying defects causing schizophrenia symptoms. NMDAR antagonists and knockout (KO) mice were used to evaluate the role of GluN2C and GluN2D NMDAR subunits in generating NMDAR antagonist-induced oscillations. We find that basal oscillatory power was elevated in GluN2C-KO mice, especially in the low gamma frequencies while there was no statistically significant difference in basal oscillations between WT and GluN2D-KO mice. Compared to wildtype (WT) mice, NMDAR channel blockers caused a greater increase in oscillatory power in GluN2C-KO mice and were relatively ineffective in inducing oscillations in GluN2D-KO mice. In contrast, preferential blockade of GluN2A-and GluN2B-containing receptors induced oscillations that did not appear to be changed in either KO animal. We propose a model wherein NMDARs containing GluN2C in astrocytes and GluN2D in interneurons serve to detect local cortical

Background: Attention selection is considered to be determined by the perceptual load of cognitive tasks and attention resources that are assigned to processingindependent stimuli. Methods:Using visual search paradigm and Schulte grid, the behavioral responses and event-related potential (ERP) of 27 pupils aged 8-11 (12 girls and 15 boys) were recorded. The subjects were asked to search for the numbers 1, 2, and 3 sequentially and locate the number 5 in the case of monochromatic (black) and bicolor (black-red) numbers. Results:We found that the sequential search task took longer than the location search task (p < .05). Furthermore, both search tasks took longer in two-color conditions than in monochromatic conditions. However, as for sequential search and location search tasks, no significant intra-group difference was found. ERP data showed that there was significant difference between monochromatic and bichromatic conditions in locating search tasks (P2-P4: p < .05; T7: p < .05, T8: p < .05), but there was no significant difference in sequential search tasks. Conclusions:Our results indicates that red will be interfered when searching for one number, but will not be interfered when searching for three numbers, which is related to the higher perceptual load of sequential search tasks and less attention resources than those used to interfere with stimulus processing.