Some pathogenic SETX variants are partially conserved during evolution

Huma Tariq; Iqra Tariq; Thomas Bourinaris; Henry Houlden; Sadaf Naz

doi:10.1016/j.gene.2020.145360

Some pathogenic SETX variants are partially conserved during evolution

Gene. 2021 Mar 1:771:145360. doi: 10.1016/j.gene.2020.145360. Epub 2020 Dec 15.

Authors

Huma Tariq¹, Iqra Tariq², Thomas Bourinaris³, Henry Houlden⁴, Sadaf Naz⁵

Affiliations

¹ Department 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. Electronic address: huma.ncvi@gmail.com.
² Khawaja Muhammad Safdar Medical College, Sialkot, Pakistan.
³ Department of Neurogenetics, UCL Institute of Neurology, Queen Square House, University College London, London, United Kingdom.
⁴ Department of Neurogenetics, UCL Institute of Neurology, Queen Square House, University College London, London, United Kingdom. Electronic address: h.houlden@ucl.ac.uk.
⁵ School of Biological Sciences, University of the Punjab, Lahore, Pakistan. Electronic address: naz.sbs@pu.edu.pk.

PMID: 33333218
DOI: 10.1016/j.gene.2020.145360

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.

Keywords: AOA2; Amino acid conservation; Ataxia; Pakistan; Senataxin.

MeSH terms

Adolescent
Amyotrophic Lateral Sclerosis / genetics*
DNA Helicases / chemistry
DNA Helicases / genetics*
Evolution, Molecular
Female
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
Male
Multifunctional Enzymes / chemistry
Multifunctional Enzymes / genetics*
Mutation, Missense*
Pedigree
Protein Domains
RNA Helicases / chemistry
RNA Helicases / genetics*
Sequence Analysis, DNA
Spinocerebellar Ataxias / congenital*
Spinocerebellar Ataxias / genetics
Young Adult

Substances

Multifunctional Enzymes
SETX protein, human
DNA Helicases
RNA Helicases

Supplementary concepts

Spinocerebellar ataxia, autosomal recessive 1