Publication year
2015Source
Journal of Internal Medicine, 278, 2, (2015), pp. 203-10ISSN
Publication type
Article / Letter to editor

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Organization
Human Genetics
Internal Medicine
Journal title
Journal of Internal Medicine
Volume
vol. 278
Issue
iss. 2
Page start
p. 203
Page end
p. 10
Subject
Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience; Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life SciencesAbstract
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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- Faculty of Medical Sciences [80037]
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