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The majority of patients with developmental and epileptic encephalopathy(DEE)has genetic causes and presents with cognitive impairment and severe seizures.Although controlling seizures cannot improve cognitive impairment,targeted therapy based on individualized factors,corrects pathological and physiological processes with clear molecular genetic mechanisms in DEE patients,thereby achieving good clinical outcomes.According to the study of the molecular genetic mechanisms of related DEE such as SCN1A,KCNQ2/KCNQ3,CDKL5 and PCDH19,gene therapy such as antisense oligonucleotides(ASOs),Ataluren,adenovirus vectors,and gene editing has shown great promise for treatment of DEE,among which ASOs demonstrate enormous potential for treatment of DEE.Next-generation sequencing technologies,animal models,inducing polyenergic stem cell technologies,organ clusters from patient cells,and gene editing technologies can promote the development of future targeted epilepsy therapies.
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Epigenetic modification genes are defined as genes whose products modify the epigenome directly through DNA methylation, histone modification or chromatin remodeling.More and more studies have shown that mutations in epigenetic modification genes are an important etiology of rare diseases with abnormal cardiac development.And these diseases usually affect multiple organs including heart due to the change of epigenetic components.Moreover, children′s lives and health are often threatened by a lack of effective drugs and complex cardiovascular malformations.This article reviews advances in molecule genetics of Tatton-Brown-Rahman syndrome, Kabuki syndrome, Rubinstein-Taybi syndrome, CHARGE syndrome and Sifrim-Hitz-Weiss syndrome, and mainly elaborates the mechanism of cardiovascular malformations caused by mutations in corresponding epigenetic modification genes, providing more comprehensive reference for clinical diagnosis and management.
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Anxiety disorders are one of the most common mental health problems, with a high burden of disease, high morbidity and poor adherence to medication. Cognitive-behavioral therapy (CBT) is an evidence-based type of psychotherapy that works well for anxiety disorders, but it differs greatly across individuals. Studies have shown that the efficacy of CBT for anxiety disorders is related to a variety of genes, and these genes play different roles in the efficacy of CBT. There are few relatively studies in China. By exploring the possible mechanism of these genes in the effect of CBT in patients with anxiety disorders, biological markers of anxiety disorders can be further explored, which can provide reference for domestic research in this field and be applied to the diagnosis and treatment of anxiety disorders. This paper summarized the efficacy of CBT in the treatment of anxiety disorders through HPA axis related genes, 5-hydroxytryptamine system related genes, monoamine oxidase system related genes, and neurodevelopmental related genes, and found that these genes were related to the efficacy of CBT in the treatment of anxiety disorders. It mainly included methylation of FK506 binding protein 5 promoter, methylation and polymorphism of 5-HT transporter gene, gene polymorphism of tryptophan hydroxylase 2, gene polymorphism of catechol oxymethyltransferase, and gene polymorphism of monoamine oxidase A, and so on. By studying the relationship between genetics and CBT efficacy in anxiety disorders, we can explore the related loop of how pathogenic genes of anxiety disorders affect CBT efficacy, further clarify the mechanism of genetic factors in the occurrence and development of anxiety disorders, and explore the genetic predictors of CBT efficacy.
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With the continuous development of bioinformatics technology and precision medicine, genetic mechanism investigations of genetic diseases including cleft lip and palate (CLP) have been getting more and more attention. Researchers have focused on the coding sequence of the genome and successfully found many CLP causative mutations, but there still remain some unsolved questions. In recent years, researchers′ vision has gradually shifted to non-protein coding region of the genome. This article reviews several coding sequence mutations, non-protein coding variants and their genetic mechanisms discovered in CLP researches.
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Congenital neutropenia (CN) is a heterogeneous group of disorders in the inherited bone marrow failure syndromes (IBMFS),characterized by a severe decrease in the number of blood neutrophils,and a maturation arrest of bone marrow progenitor cells mainly at the promyelocyte/myeloid stage,and most of congenital neutropenia patients are susceptibility to bacterial infections in clinically.In recent years,the mutations in ELANE,GFI1,HAX1,G6PC3,WAS,CSF3R and so on are associated with the occurrence and development of CN,and with the further research,more new virulence gene will be found gradually.
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Objective To explore the genetic mechanism of Yang-deficiency constitution by detecting genomic copy number variations (CNVs). Methods Thirty cases of Yang-deficiency constitution and 30 cases of balanced constitution were included according to the standards of Classification and Determination of Constitution in Traditional Chinese Medicine. DNA was extracted from white blood cells in peripheral blood. A genome-wide association study was conducted by using Affymetrix SNP 6.0 platform. CNVs of each sample were analyzed using PennyCNV software. The Yang-deficiency constitution-specific copy number variation regions (CNVRs) of each autosome were identified. CNVR-related genes and their annotations were searched at online Human Genome Browser. Results The mean number of CNVs in balanced constitution group was 12.63±3.39, ranging from 8 to 20. After stepwise elimination of two Yang-deficiency constitution subjects, the mean number of CNVs in Yang-deficiency constitution group was 15.04±8.95, ranging from 2 to 38. A total of 26 CNVRs were identified from 28 Yang-deficiency constitution subjects, including 19 duplicated CNVRs, 6 deleted CNVRs, and 1 mixed type CNVR. Most CNVRs were shared by a few Yang-deficiency constitution subjects, and only 7 CNVRs were shared by more than 5 Yang-deficiency constitution subjects. The functions of representative genes in Yang-deficiency constitution-specific CNVRs were related with extracellular and intracellular signal transduction, metabolic regulation, and immune response, etc. Conclusion Yang-deficiency constitution subjects have some specific genomic CNVs, which might result in Yang-deficiency constitution phenotypes by influencing the expression of genes associated with extracellular and intracellular signal transduction, material metabolism (energy metabolism), and immune response, etc.