National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, 410083, Hunan, China.
Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410083, Hunan, China.
Mol Neurobiol. 2021 Aug;58(8):3863-3873. doi: 10.1007/s12035-021-02377-y. Epub 2021 Apr 15.
Neurodevelopmental disorders (NDDs) are a group of diseases characterized by high heterogeneity and frequently co-occurring symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1102 patients with NDDs and validated 1271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes. Notably, 36 of these 78 genes are the first to be reported in Chinese patients with NDDs. By integrating our genetic data with public data, we prioritized 212 NDD candidate genes with FDR < 0.1, including 17 novel genes. The novel candidate genes interacted or were co-expressed with known candidate genes, forming a functional network involved in known pathways. We highlighted MSL2, which carried two de novo protein-truncating variants (p.L192Vfs3 and p.S486Ifs11) and was frequently connected with known candidate genes. This study provides the mutational spectrum of NDDs in China and prioritizes 212 NDD candidate genes for further functional validation and genetic counseling.
神经发育障碍（NDD）是一组具有高度异质性且常伴有多种症状的疾病。NDD 患者的突变谱在很大程度上并不完整。在此，我们对 1102 名 NDD 患者的 547 个基因进行了测序，并验证了 1271 个潜在的功能变异体，包括 78 个常染色体基因中的 108 个新生变异体（DNV）和 6 个 X 染色体基因中的 7 个遗传半合子变异体。值得注意的是，其中 36 个基因是首次在中国 NDD 患者中报道的。通过整合我们的遗传数据和公共数据，我们确定了 212 个 FDR<0.1 的 NDD 候选基因，其中包括 17 个新基因。这些新的候选基因与已知的候选基因相互作用或共表达，形成了一个涉及已知途径的功能网络。我们重点介绍了 MSL2，该基因携带两个新生蛋白截断变异体（p.L192Vfs3 和 p.S486Ifs11），并且经常与已知的候选基因相关联。本研究提供了中国 NDD 的突变谱，并确定了 212 个 NDD 候选基因，以进一步进行功能验证和遗传咨询。
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