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Updated: Apr 18, 2026
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
A missense mutation underlies defective SOCS4 function in a family with autoimmunity
P Arts1, T S Plantinga2, J M van den Berg3
1Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Donders Centre for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands.
Objective:
The aim of this study was to determine the genetic and immunological defects underlying familial manifestations of an autoimmune disorder.
Methods:
Whole-exome sequencing was performed on the index patient with various manifestations of autoimmunity, including hypothyroidism, vitiligo and alopecia. Peripheral blood mononuclear cells and DNA of family members were used for functional and genetic testing of the candidate variants obtained by Sanger sequencing.
Results:
Exome sequencing identified 233 rare, coding and nonsynonymous variants in the index patient; five were highly conserved and affect genes that have a possible role in autoimmunity. Only a heterozygous missense mutation in the suppressor of cytokine signalling 4 gene (SOCS4) cosegregated with the autoimmune disorder in the family. SOCS4 is a known inhibitor of epidermal growth factor (EGF) receptor signalling, and functional studies demonstrated specific upregulation of EGF-dependent immune stimulation in affected family members.
Conclusion:
We present a family with an autoimmune disorder, probably resulting from dysregulated immune responses due to mutations in SOCS4.
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