Gogate Ashlesha, Kaur Kiran, Khalil Raida, Bashtawi Mahmoud, Morris Mary Ann, Goodspeed Kimberly, Evans Patricia, Chahrour Maria H
Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Department of Biotechnology and Genetic Engineering, Faculty of Science, University of Philadelphia, Amman, Jordan.
NPJ Genom Med. 2024 Dec 4;9(1):62. doi: 10.1038/s41525-024-00444-6.
Autism spectrum disorder (ASD) comprises neurodevelopmental disorders with wide variability in genetic causes and phenotypes, making it challenging to pinpoint causal genes. We performed whole exome sequencing on a modest, ancestrally diverse cohort of 195 families, including 754 individuals (222 with ASD), and identified 38,834 novel private variants. In 68 individuals with ASD (~30%), we identified 92 potentially pathogenic variants in 73 known genes, including BCORL1, CDKL5, CHAMP1, KAT6A, MECP2, and SETD1B. Additionally, we identified 158 potentially pathogenic variants in 120 candidate genes, including DLG3, GABRQ, KALRN, KCTD16, and SLC8A3. We also found 34 copy number variants in 31 individuals overlapping known ASD loci. Our work expands the catalog of ASD genetics by identifying hundreds of variants across diverse ancestral backgrounds, highlighting convergence on nervous system development and signal transduction. These findings provide insights into the genetic underpinnings of ASD and inform molecular diagnosis and potential therapeutic targets.
自闭症谱系障碍（ASD）是一类神经发育障碍，其遗传病因和表型具有广泛的变异性，这使得确定致病基因具有挑战性。我们对一个规模适中、具有不同祖先背景的195个家庭的队列（包括754名个体，其中222名患有ASD）进行了全外显子测序，共鉴定出38,834个新的私有变异。在68名患有ASD的个体（约占30%）中，我们在73个已知基因中鉴定出92个潜在的致病变异，这些基因包括BCORL1、CDKL5、CHAMP1、KAT6A、MECP2和SETD1B。此外，我们在120个候选基因中鉴定出158个潜在的致病变异，这些基因包括DLG3、GABRQ、KALRN、KCTD16和SLC8A3。我们还在31名个体中发现了34个与已知ASD基因座重叠的拷贝数变异。我们的工作通过在不同祖先背景中鉴定数百个变异，扩展了ASD遗传学的目录，突出了在神经系统发育和信号转导方面的趋同性。这些发现为ASD的遗传基础提供了见解，并为分子诊断和潜在的治疗靶点提供了依据。
