Some pathogenic SETX variants are partially conserved during evolution
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Updated: Nov 25, 2025

Following the Dynamics of Structural Variants in Experimentally Evolved Populations
Published on: February 3, 2023
Huma Tariq1, Iqra Tariq2, Thomas Bourinaris3
1Department of Neurogenetics, UCL Institute of Neurology, Queen Square House, University College London, London, United Kingdom; School of Biological Sciences, University of the Punjab, Lahore, Pakistan.
Abstract:
Variants in SETX have been implicated in recessively and dominantly inherited disorders, ataxia with oculomotor apraxia type 2 (AOA2 OMIM# 606002) and amyotrophic lateral sclerosis (ALS4, OMIM# 602433) respectively, in humans. We report two novel bi-allelic pathogenic variants in SETX in patients suffering from ataxia with oculomotor apraxia type 2, extending the allelic spectrum of the gene variants. We also discuss the pathogenicity of SETX variants in relation to the evolutionary conservation status of the affected amino acids. Our analyses suggest that variants of some amino acids which are not fully conserved in evolution, may cause a disorder in humans, provided the particular pathogenic variant is absent in other orthologues.
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