{"title":"TBL1XR1的不同突变导致神经发育障碍的不同表型:两例报告。","authors":"Linlin Wei, Yonghui Yang, Tiejia Jiang, Chaolang Zhang, Cuiying Chen, Mingwei Huang, Nannan Li, Huachun Xiong, Feng Gao","doi":"10.1186/s12920-025-02169-6","DOIUrl":null,"url":null,"abstract":"<p><p>The TBL1XR1 gene (Transducin beta-like 1X-linked receptor 1) is responsible for encoding the TBL1XR1 protein, an important component of the NCoR and SMRT corepressor complexes. 48 missense variants of the TBL1XR1 gene have been reported, which are associated with various phenotypes of neurodevelopmental disorders, including West syndrome, Pierpont syndrome, and others. However, given the important role of TBL1XR1 in neurological diseases, it is still necessary to further explore the variation of TBL1XR1. In this study, we present two patients with distinct variants and phenotypes. Patient 1 exhibits global developmental delay, intellectual disability, delayed language development, and seizures. While patient 2 displays mild facial dysmorphism, significant developmental delay, feeding difficulties, and increased muscle tone. Through trio whole-exome sequencing, two novel pathogenic variants in the TBL1XR1 gene were identified: A heterozygous NM_024665.6:c.940G > T (p.Val314Phe) variant in patient 1 and a heterozygous NM_024665.6:c.1387G > T (p.Asp463Tyr) in patient 2. Discovery of these two novel variant sites expands the mutation spectrum associated with the TBL1XR1 gene.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"96"},"PeriodicalIF":2.1000,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Different mutations in TBL1XR1 lead to diverse phenotypes of neurodevelopmental disorder: two case reports.\",\"authors\":\"Linlin Wei, Yonghui Yang, Tiejia Jiang, Chaolang Zhang, Cuiying Chen, Mingwei Huang, Nannan Li, Huachun Xiong, Feng Gao\",\"doi\":\"10.1186/s12920-025-02169-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The TBL1XR1 gene (Transducin beta-like 1X-linked receptor 1) is responsible for encoding the TBL1XR1 protein, an important component of the NCoR and SMRT corepressor complexes. 48 missense variants of the TBL1XR1 gene have been reported, which are associated with various phenotypes of neurodevelopmental disorders, including West syndrome, Pierpont syndrome, and others. However, given the important role of TBL1XR1 in neurological diseases, it is still necessary to further explore the variation of TBL1XR1. In this study, we present two patients with distinct variants and phenotypes. Patient 1 exhibits global developmental delay, intellectual disability, delayed language development, and seizures. While patient 2 displays mild facial dysmorphism, significant developmental delay, feeding difficulties, and increased muscle tone. Through trio whole-exome sequencing, two novel pathogenic variants in the TBL1XR1 gene were identified: A heterozygous NM_024665.6:c.940G > T (p.Val314Phe) variant in patient 1 and a heterozygous NM_024665.6:c.1387G > T (p.Asp463Tyr) in patient 2. Discovery of these two novel variant sites expands the mutation spectrum associated with the TBL1XR1 gene.</p>\",\"PeriodicalId\":8915,\"journal\":{\"name\":\"BMC Medical Genomics\",\"volume\":\"18 1\",\"pages\":\"96\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Medical Genomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12920-025-02169-6\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Medical Genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12920-025-02169-6","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
TBL1XR1基因(转导蛋白β样1x连接受体1)负责编码TBL1XR1蛋白,该蛋白是nor和SMRT辅抑制因子复合物的重要组成部分。已经报道了48种TBL1XR1基因错义变异,它们与神经发育障碍的各种表型相关,包括West综合征、Pierpont综合征等。然而,鉴于TBL1XR1在神经系统疾病中的重要作用,仍有必要进一步探索TBL1XR1的变异。在本研究中,我们介绍了两例具有不同变异和表型的患者。患者1表现为整体发育迟缓、智力残疾、语言发育迟缓和癫痫发作。患者2表现为轻度面部畸形,明显发育迟缓,进食困难,肌张力增高。通过三重奏全外显子组测序,鉴定出TBL1XR1基因的两个新的致病变异:一个杂合的NM_024665.6:c;患者1的940G > T (p.Val314Phe)变异和杂合NM_024665.6:c。1387G > T (p.Asp463Tyr),患者2。这两个新的变异位点的发现扩大了与TBL1XR1基因相关的突变谱。
Different mutations in TBL1XR1 lead to diverse phenotypes of neurodevelopmental disorder: two case reports.
The TBL1XR1 gene (Transducin beta-like 1X-linked receptor 1) is responsible for encoding the TBL1XR1 protein, an important component of the NCoR and SMRT corepressor complexes. 48 missense variants of the TBL1XR1 gene have been reported, which are associated with various phenotypes of neurodevelopmental disorders, including West syndrome, Pierpont syndrome, and others. However, given the important role of TBL1XR1 in neurological diseases, it is still necessary to further explore the variation of TBL1XR1. In this study, we present two patients with distinct variants and phenotypes. Patient 1 exhibits global developmental delay, intellectual disability, delayed language development, and seizures. While patient 2 displays mild facial dysmorphism, significant developmental delay, feeding difficulties, and increased muscle tone. Through trio whole-exome sequencing, two novel pathogenic variants in the TBL1XR1 gene were identified: A heterozygous NM_024665.6:c.940G > T (p.Val314Phe) variant in patient 1 and a heterozygous NM_024665.6:c.1387G > T (p.Asp463Tyr) in patient 2. Discovery of these two novel variant sites expands the mutation spectrum associated with the TBL1XR1 gene.
期刊介绍:
BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.