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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2024

Open Access 01-12-2024 | Disorders of Intellectual Development | Research

The spectrum of neurological presentation in individuals affected by TBL1XR1 gene defects

Authors: Amanda Nagy, Francine Molay, Sarah Hargadon, Claudia Brito Pires, Natalie Grant, Lizbeth De La Rosa Abreu, Jin Yun Chen, Precilla D’Souza, Ellen Macnamara, Cynthia Tifft, Catherine Becker, Claudio Melo De Gusmao, Vikram Khurana, Ann M. Neumeyer, Florian S. Eichler

Published in: Orphanet Journal of Rare Diseases | Issue 1/2024

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Abstract

Background

TBL1XR1 encodes a F-box-like/WD40 repeat-containing protein that plays a role in transcription mediated by nuclear receptors and is a known genetic cause of neurodevelopmental disease of childhood (OMIM# 608628). Yet the developmental trajectory and progression of neurologic symptoms over time remains poorly understood.

Methods

We developed and distributed a survey to two closed Facebook groups devoted to families of patients with TBL1XR1-related disorder. The survey consisted of 14 subsections focused upon the developmental trajectories of cognitive, behavioral, motor, and other neurological abnormalities. Data were collected and managed using REDCap electronic data capture tools.

Results

Caregivers of 41 patients with a TBL1XR1-related disorder completed the cross-sectional survey. All reported variants affecting a single amino acid, including missense mutations and in-frame deletions, were found in the WD40 repeat regions of Tbl1xr1. These are domains considered important for protein–protein interactions that may plausibly underlie disease pathology. The majority of patients were diagnosed with a neurologic condition before they received their genetic diagnosis. Language appeared most significantly affected with only a minority of the cohort achieving more advanced milestones in this domain.

Conclusion

TBL1XR1-related disorder encompasses a spectrum of clinical presentations, marked by early developmental delay ranging in severity, with a subset of patients experiencing developmental regression in later childhood.
Appendix
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Metadata
Title
The spectrum of neurological presentation in individuals affected by TBL1XR1 gene defects
Authors
Amanda Nagy
Francine Molay
Sarah Hargadon
Claudia Brito Pires
Natalie Grant
Lizbeth De La Rosa Abreu
Jin Yun Chen
Precilla D’Souza
Ellen Macnamara
Cynthia Tifft
Catherine Becker
Claudio Melo De Gusmao
Vikram Khurana
Ann M. Neumeyer
Florian S. Eichler
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2024
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-024-03083-3

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