Recently, a paper entitled DYRK1A nonsense mutation associated with autism affects the development of cortex and neuronal dendrites and dendritic spines was published on Molecular Psychiatry, an international authoritative journal in mental diseases. It is the collaborated result of Boston Children's Hospital, Professor Wu Bolin’s team from Children’s Hospital affiliated to Fudan University, and Professor Qiu Zilong’s team from Shanghai Institute for Biological Sciences affiliated to the Chinese Academy of Science (CAS).
According to their work, twelve genetic mutations of DYRK1A were screened from 892 patients diagnosed with autism spectrum disorders. Then, through constructing 5 different DYRK1A mutants, their functions in the development of cortex and the growth of neuronal cells were explored, showing that DYRK1A played an important role in neuro-development. DYRK1A dysfunction or abnormal function would result in the defects like dendritic growth, development of dendritic spines and radial migration. In addition, two nonsense mutations were found to cause dysfunction of the DYRK1A protein. For the first time, scientists revealed the key significance of a decreasing dose of the DYRK1A protein on postnatal neurodevelopments, laying a foundation for the further study of the protein and the pathogenesis of autism.
Autism is a complicated hereditary syndrome and neuropsychiatric disorder, with noticeable signs in early childhood. Its clinical diagnosis can be confirmed by three typical features: impaired social interaction, repetitive behavioral patterns and impaired verbal communication. So far, no effective treatment has been found, wihle higher prevalence of autism arouses public concern these years. Clinical and basic research on autism and related animal models are key issues in the field of medicine and neuroscience nowadays.
DYRK1A has been identified as one of candidate genes causing autism in recent years. The gene is well-known by its important role in Down’s syndrome. Past researches mainly concentrated on the correlation between the triple type of the gene and neurodevelopmental abnormalities, meaning that the gain of function of DYRK1A protein results in mental retardation. But a new exon data showed that DYRK1A mutations are detected in autism patients. The correlation between DYRK1A and autism is a question to be solved. The research found two nonsense mutations resulting in loss of DYRK1A expression and proved that the loss of function of the DYRK1A protein could cause autism.
The research was done by Doctor Dang Ting instructed by Professor Wu and Researcher Qiu. Members in the research group played an active role, supported by Boston Children’s Hospital of Harvard University.
