ABSTRACT
OBJECTIVE@#To analyze the clinical and genetic characteristics in a girl with 2q37 deletion syndrome.@*METHODS@#Genomic DNA was extracted from peripheral blood samples taken from the patient and her parents, and was subjected to whole exome sequencing (WES) and low-coverage massively parallel copy number variation sequencing (CNV-seq). Candidate CNVs were verified by chromosomal karyotyping analysis and fluorescence quantitative PCR.@*RESULTS@#The child was found to harbor a 6 Mb heterozygous deletion in 2q37 by WES and CNV-seq. The deletion has encompassed 98 genes with a range from GBX2 to LINC01881, and was de novo in origin. The result of fluorescence quantitative PCR was consistent with that of WES and CNV-seq. However, karyotyping analysis has failed to detect the deletion.@*CONCLUSION@#The patient was diagnosed with 2q37 deletion syndrome. Combined WES and CNV-seq method features high resolution, high throughput, and high sensitivity, which can significant raise the diagnostic rate for patients with mental disorder, multiple malformations and unknown syndromes.
ABSTRACT
Objective To explore the effects of Ginkgolide B on the expression of hypoxia inducible factor 1 α (HIF-1α) and P I3K/Akt pathway in the hippocampus of developing rats after pentylenetetrazol(PTZ)-induced status epilepticus,and to investigate the correlation between HIF-1α expression and PI3K/Akt pathway.Methods Ninety-six SD rats aged 21 days were randomly divided into normal saline group(group NS),status epilepticus group (group P),GKB treatment groups (group G+P),GKB +wortmannin treated group (group G+P+W),wortmannin treated group(group P+W).The brain tissue were harvested from the rats at 4 and 8 hours after the inducement,but in the group G+P at 1 h,4 h,8 h,24 h.Immunohistochemistry and Western blot were used respectively to detect HIF-1α and p-Akt protein expression.Results (1) For the group G+P,there were statistical differences in the expression levels of p-Akt protein between 1 h,4 h,8 h and 24 h(P＜0.01),The p-Akt protein reached the peak level at 4 hours (0.85±0.03),there were statistical differences in the expression levels of HIF-1α protein between 1 h,4 h,8 h and 24 h(P＜0.01),the HIF-1α expression reached the peak level at 8 hours(1.00±0.13).(2) The expression of HIF-1α in all the groups at 8 hours time point:the expression levels of HIF-1α in the group P and group G+P were significantly higher than those in the group NS (P＜0.01) and the expression levels of HIF1α in the group G+P were higher than those in the group P(P＜0.01).Using wortmannin,the PI3K/Akt specific inhibitor,HIF-1α protein expression in the group G+P+W and P+W was significantly decreased when compared with the group G+P and P (P＜0.01).(3)The expression of p-Akt in all the groups at 4 hours time point:the expression levels of p-Akt in the group P and group G+P were significantly higher than those in the group NS (P＜0.01) and the expression levels of p-Akt in the group G+P were higher than those in the group P (P＜ 0.01).Using wortmannin,p-Akt protein expression in the group G+P+W and P+W was significantly decreased when compared with the group G+P and P (P＜0.01).Conclusion GKB can activate PI3K/Akt signaling pathway,and the pathway is involved in regulating the expression of HIF-1α.