Recently, the international authoritative academic journals Science Advances and Nature Communications successively published three international cooperation research results of the research team led by Xia Kun (Researcher) and Guo Hui (Associate Researcher) from the Center for Medical Genetics of the School of Life Sciences of Central South University, which plays an important role in understanding the molecular typing of autism spectrum disorder (ASD) and the pathogenesis of autism.
The paper entitled "Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission" reveals that CSDE1-binding target RNAs are significantly enriched in autism- and growth retardation-associated genes, and especially fragile X syndrome (another autism-associated syndrome) pathogenic gene-encoded protein FRMP target RNAs, which indicates that the autism might have similar pathogenic mechanism as that of fragile X syndrome, and the intervention and treatment strategies associated with fragile X syndrome might also have significant intervention and treatment effects on patients with CSDE1 mutation. Analyses of a series ofin vitrocultured neurons and Drosophila models indicate that loss of CSDE1 function plays an essential role in neuronal development and synaptic function. These results suggest that CSDE1 may affect neuronal development and synaptic function and further lead to the occurrence of autism and related neurodevelopmental phenotypes through post-transcriptional regulation of multiple autism-associated risk genes.
The paper entitled "Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders" discovers 20 worldwide patients with disruptive mutations in TANC2, through large-scale international cooperation. Detailed genotype-phenotype correlation analysis finds that patients with mutations in TANC2 generally present with autism or autism-like symptoms, cognitive dysfunction, delayed language and motor development, epilepsy and other phenotypes, defining a new autism-associated neurodevelopmental syndrome from the perspective of clinical genetics. In addition, the researchers observe a pattern of complex psychiatric dysfunction or behavioral problems in more than half of adult probands and carrier parents, which provides important clues to explain the common genetic basis and pathogenesis of neurodevelopmental and psychiatric disorders.
The paper entitled "AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders" clarifies, for the first time through the cooperation of 56 units worldwide, that de-novo variants in GRIA2 can cause a new neurodevelopmental disorder. GRIA2 encodes the four subunits of AMPA ionotropic glutamate receptor, including GRIA1, GRIA2, GRIA3 and GRIA4. In recent years, GRIA1, GRIA3 and GRIA4 have been reported to cause autism and other neurodevelopmental diseases, but the correlation between GRIA2 mutation and neurodevelopmental diseases has not been elucidated. The research team led by Xia Kun and Guo Hui began to ascertain the sequence of this GRIA2 gene in Chinese autistic patients in 2014, and successively found 4 patients with de-novo variants in GRIA2, suggesting that this gene is highly correlated with the onset of autism. Through cooperation with the research team led by Henry Houlden and Dimitri M. Kullmann from University College London and a number of units from around the world, 28 patients affected with neurodevelopmental diseases carrying de-novo variants in GRIA2 were discovered. Electrophysiological studies reveal that the de-novo variants in GRIA2 could lead to dysfunction of GRIA2 protein, and from the perspective of clinical genetics, show de-novo variants in GRIA2 could lead to a new neurodevelopmental disease.
The research team led by Xia Kun and Guo Hui is mainly devoted to studying the genetic basis and pathogenesis of autism and related neurodevelopmental diseases. Through more than 10 years of accumulation, Chinese library of clinical genetic resources for autism has been established. In the field of genetic basis and pathogenesis of autism, the group has published a series of important research results in international authoritative journals such as Science Advances, Molecular Psychiatry (2 papers), Nature Communications (3 papers), Cell Research, Genetics In Medicine, Cell Reports, and Molecular Autism, as the first author or the corresponding author. These results play an important role in understanding the genetic structure, early diagnosis, risk warning, and precise diagnosis and treatment of autism, especially Chinese autism. The above researches obtain the support from the National Basic Research Program (973 Program), the National Science Fund for Distinguished Young Scholars, the Key Program of the National Natural Science Foundation of China, the General Program of National Natural Science Foundation of China, the Central South University Innovation Drive Program, and the Hunan Provincial Key Research and Development Program.
Source: College of Life Sciences