Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Alper Center for Neural Development and Regeneration, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Alper Center for Neural Development and Regeneration, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Curr Opin Neurobiol. 2024 Oct;88:102902. doi: 10.1016/j.conb.2024.102902. Epub 2024 Aug 20.
A significant source of risk for neurodevelopmental disorders (NDDs), including intellectual disability (ID) and autism spectrum disorder (ASD), lies in genes located on the X chromosome. Males can be particularly vulnerable to X-linked variation because of hemizygosity, and male-specific segregation in pedigrees has guided earlier gene discovery for X-linked recessive conditions. More recently, X-linked disorders disproportionally affecting females, with complex inheritance patterns and/or presenting with sex differences, have surfaced. Here, we discuss the genetics and neurobiology of X-linked genes that are paradigmatic to understand NDDs in females. Integrating genetic, clinical, and functional data will be key to understand how X-linked variation contributes to the risk architecture of NDDs.
X 染色体上的基因是神经发育障碍（NDD），包括智力障碍（ID）和自闭症谱系障碍（ASD）的重要风险源。由于半合子状态，男性特别容易受到 X 连锁变异的影响，而家系中的男性特异性分离则指导了 X 连锁隐性疾病的早期基因发现。最近，不成比例地影响女性的 X 连锁疾病、具有复杂遗传模式和/或表现出性别差异的 X 连锁疾病已经出现。在这里，我们讨论了 X 连锁基因的遗传学和神经生物学，这些基因是理解女性 NDD 的典范。整合遗传、临床和功能数据将是理解 X 连锁变异如何导致 NDD 风险结构的关键。
