Genotype and Phenotype Correlations for TBL1XR1 in Neurodevelopmental Disorders
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Genotype and Phenotype Correlations for TBL1XR1 in Neurodevelopmental Disorders Yingting Quan 1 & Qiumeng Zhang 1 & Meilin Chen 1 & Huidan Wu 1 & Jianjun Ou 2 & Yidong Shen 2 & Kuokuo Li 1 & Guanglei Xun 3 & Jingping Zhao 2 & Zhengmao Hu 1 & Kun Xia 1,4 & Hui Guo 1,5 Received: 1 February 2020 / Accepted: 25 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract TBL1XR1 is a member of the WD40 repeat-containing gene family. Mutations of TBL1XR1 have been reported in neurodevelopmental disorders (NDDs). Although the phenotypes of some patients have been described in single studies, few studies have reviewed the genotype and phenotype relationships using a relatively large cohort of patients with TBL1XR1 mutations. Herein, we report a new de novo frameshift mutation in TBL1XR1 (NM_024665.4, c.388_389delAC, p.T130Sfs*14) in a patient with autism spectrum disorder (ASD). To explore the correlations between genotypes and phenotypes for TBL1XR1 in NDDs, we manually curated and analyzed 38 variants and the associated phenotypes from 50 individuals with NDDs. TBL1XR1 mutations lead to a wide range of phenotypic defects. We conclude that the most common phenotypes associated with TBL1XR1 mutations were language and motor developmental delay, intellectual disabilities, facial deformity, hypotonia, and microcephaly. Our study provides a comprehensive spectrum of neurodevelopmental phenotypes caused by TBL1XR1 mutations, which is important for genetic diagnosis and precision clinical management. Keywords TBL1XR1 . Neurodevelopmental disorder . Autism spectrum disorder . De novo mutation . Genotype-phenotype correlation
Introduction TBL1XR1, a member of the WD40 repeat-containing gene family, was first reported as a causative gene of Pierpont Yingting Quan and Qiumeng Zhang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12031-020-01615-7) contains supplementary material, which is available to authorized users. * Hui Guo [email protected] 1
Center for Medical Genetics & Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
2
Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
3
Mental Health Center of Shandong Province, Jinan, Shandong, China
4
Collaborative Innovation Center for Genetics and Development, Shanghai, China
5
Hunan Key Laboratory of Animal Models for Human Diseases, Changsha 410078, China
syndrome (Heinen et al. 2016), which is characterized by physical developmental delay and facial deformity, such as frontal bossing, midface hypoplasia, depressed nasal bridge, plantar fat pads, decreased hearing, and short stature (Pierpont et al. 1998). TBL1XR1, encoded by TBL1XR1, is a WD40containing factor. TBL1XR1 binds with the silencing mediator of the retinoic acid/thyroid hormone receptor (NCoR/SMRT) (Perissi et al. 2004) and interacts with nuclear hormone receptors to modu
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