Different mutations in TBL1XR1 lead to diverse phenotypes of neurodevelopmental disorder: two case reports

Abstract 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 neuro...

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Main Authors: Linlin Wei, Yonghui Yang, Tiejia Jiang, Chaolang Zhang, Cuiying Chen, Mingwei Huang, Nannan Li, Huachun Xiong, Feng Gao
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Medical Genomics
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Online Access:https://doi.org/10.1186/s12920-025-02169-6
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author Linlin Wei
Yonghui Yang
Tiejia Jiang
Chaolang Zhang
Cuiying Chen
Mingwei Huang
Nannan Li
Huachun Xiong
Feng Gao
author_facet Linlin Wei
Yonghui Yang
Tiejia Jiang
Chaolang Zhang
Cuiying Chen
Mingwei Huang
Nannan Li
Huachun Xiong
Feng Gao
author_sort Linlin Wei
collection DOAJ
description Abstract 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.
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institution Kabale University
issn 1755-8794
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publishDate 2025-05-01
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spelling doaj-art-e3da2e9e2b1d433791111f7f068f00c82025-08-20T04:02:41ZengBMCBMC Medical Genomics1755-87942025-05-011811710.1186/s12920-025-02169-6Different mutations in TBL1XR1 lead to diverse phenotypes of neurodevelopmental disorder: two case reportsLinlin Wei0Yonghui Yang1Tiejia Jiang2Chaolang Zhang3Cuiying Chen4Mingwei Huang5Nannan Li6Huachun Xiong7Feng Gao8Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthThe Third Affiliated Hospital of Zhengzhou UniversityChildren’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthChildren’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthChildren’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthAegicare (Shenzhen) Technology Co. LtdAegicare (Shenzhen) Technology Co. LtdThe Third Affiliated Hospital of Zhengzhou UniversityChildren’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthAbstract 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.https://doi.org/10.1186/s12920-025-02169-6TBL1XR1Trio-WESMRD41Case reportsPierpont syndrome
spellingShingle Linlin Wei
Yonghui Yang
Tiejia Jiang
Chaolang Zhang
Cuiying Chen
Mingwei Huang
Nannan Li
Huachun Xiong
Feng Gao
Different mutations in TBL1XR1 lead to diverse phenotypes of neurodevelopmental disorder: two case reports
BMC Medical Genomics
TBL1XR1
Trio-WES
MRD41
Case reports
Pierpont syndrome
title Different mutations in TBL1XR1 lead to diverse phenotypes of neurodevelopmental disorder: two case reports
title_full Different mutations in TBL1XR1 lead to diverse phenotypes of neurodevelopmental disorder: two case reports
title_fullStr Different mutations in TBL1XR1 lead to diverse phenotypes of neurodevelopmental disorder: two case reports
title_full_unstemmed Different mutations in TBL1XR1 lead to diverse phenotypes of neurodevelopmental disorder: two case reports
title_short Different mutations in TBL1XR1 lead to diverse phenotypes of neurodevelopmental disorder: two case reports
title_sort different mutations in tbl1xr1 lead to diverse phenotypes of neurodevelopmental disorder two case reports
topic TBL1XR1
Trio-WES
MRD41
Case reports
Pierpont syndrome
url https://doi.org/10.1186/s12920-025-02169-6
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