基因与脑发育障碍研究

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　　More than 11,700 affected⁵ individuals and nearly 2,800 control subjects underwent targeted DNA⁶ sequencing of 208 suspected disease-risk genes⁸, which were chosen based on previously⁹ published studies. By looking at greater numbers of cases and using a reliable yet inexpensive molecular¹⁰ inversion¹¹ probe, the project team wanted to measure the statistical¹² significance of individual, implicated¹³ genes.

　　Led by Holly¹⁴ A. F. Stessman, Bo Xiong and Bradley P. Coe, of the genome sciences laboratory of Evan Eichler at the University of Washington School of Medicine and the Howard Hughes Medical Institute and reported in Nature Genetics, samples were collected through the Autism Spectrum¹⁶/Intellectual Disability 15-center network spanning seven countries and four continents. An advantage of this collection, the researchers said, is the ability to check back on a large fraction of cases to try to relate genetic¹⁵ results to clinical findings.

　　New study to sort out risk genes for brain development disorders

　　In their study population, the researchers associated 91 genes with the risk of a neurodevelopmental disorder². These included 38 genes not previously suspected of playing a role. Based on some of the family studies, however, mutations even in two or more of the risk genes may not be necessary or sufficient to cause disease. Of the 91 genes, 25 were linked with forms of autism without intellectual disability. The researchers also described a gene⁷ network that appeared to be related to high-functioning autism. Individuals with this form of autism have average to above average intelligence, but may struggle in learning to talk, interact socially, or manage anxiety and sensory¹⁷ overload¹⁸.

　　While observing that some genes were more closely associated with autism and others with intellectual or developmental impairments, the researchers found that most of the genes implicated were mutated in both conditions. "Most of these genes are clearly risk factors for neurodevelopmental disorders in a broad sense," the researchers explained. "But analysis of both the genetic and subsequent patient follow-up data did single out some genes with a statistical bias¹⁹ towards autism spectrum disorder, rather than an intellectual disability or developmental delay."

　　This result reinforces the substantial overlap²⁰ among these conditions in their underlying genetics and observable characteristics. And additional findings suggest that less severe mutations may be behind autism that is not accompanied by intellectual disability. In addition to looking at the overall severity of each neurodevelopmental disorder present, the researchers summarized other features such as seizures²¹, head size, and congenital abnormalities.

　　The researchers did in fact observe patterns from combining clinical and genetic data. They partitioned those genes most strongly associated with autism, and those more related to developmental disabilities. Although the overall numbers were low, several autism risk genes appeared predominantly in males, including some detected exclusively in males who had autism without intellectual impairment.

　　By following up with patients, the researchers could start to assess the newly discovered mutations. Such clinical information is important in determining how the genes might function, and how their disruption might lead to specific traits or symptoms. "The scientists are continuing this project and are eager to work with interested families," Raphael Bernier, associate professor of psychiatry²² and behavioral sciences and clinical director of the Seattle Children's Autism Center and associate director of the UW Center on Human Development and Disability, was quoted as saying in a news release.

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