Biallelic in-frame deletion of SOX4 is associated with developmental delay, hypotonia and intellectual disability

Intellectual disability (ID) represents an extremely heterogeneous group of disorders, characterized by significant limitations in intellectual function and adaptive behavior. Among the monogenic causes, autosomal recessive genes (ARID) are responsible for more than 50% of ID. Here, we report a nove...

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Published inEuropean journal of human genetics : EJHG Vol. 30; no. 2; pp. 243 - 247
Main Authors Ghaffar, Amama, Rasheed, Faiza, Rashid, Muhammad, van Bokhoven, Hans, Ahmed, Zubair M., Riazuddin, Sheikh, Riazuddin, Saima
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.02.2022
Springer International Publishing
Subjects
Autosomal recessive inheritance
Brief Communication
Doublecortin protein
Gene deletion
Genes, Recessive
Homozygote
Humans
Intellectual disabilities
Intellectual Disability - genetics
Muscle Hypotonia - genetics
Neurogenesis
Pakistan
Protein structure
Secondary structure
Sequence Deletion
SOXC Transcription Factors - genetics
Telencephalon
Transcription
Pakistan
Online AccessGet full text
ISSN1018-4813
1476-5438
1476-5438
DOI10.1038/s41431-021-00968-w

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Summary:Intellectual disability (ID) represents an extremely heterogeneous group of disorders, characterized by significant limitations in intellectual function and adaptive behavior. Among the monogenic causes, autosomal recessive genes (ARID) are responsible for more than 50% of ID. Here, we report a novel in-frame homozygous deletion variant [c.730_753del; p.(Ala244_Gly251del)] in SOX4 (sex-determining region Y-related high-mobility group box 4), segregating with moderate to severe ID, hypotonia, and developmental delay in a Pakistani family. Our identified variant p.(Ala244_Gly251del) is predicted to remove evolutionarily conserved residues from the interdomain region and may destabilize the protein secondary structure. SOX4 belongs to group C of the SOX transcription regulating family known to be involved in early embryo development. Single-cell RNA data analysis of developing telencephalon revealed highly overlapping expression of SOX4 with SOX11 and DCX, known neurogenesis regulators. Our study expands the mutational landscape of SOX4 and the repertoire of the known genetic causes of ARID.
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ISSN:1018-4813
1476-5438
1476-5438
DOI:10.1038/s41431-021-00968-w