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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Autoimmunity, Child, DNA, Exome, Family, Female, Genetic Predisposition to Disease, Genetic Testing, Hashimoto Disease, Humans, Male, Mutation, Missense, Pedigree, Sequence Analysis, DNA, Suppressor of Cytokine Signaling Proteins, Thyroiditis, Autoimmune.
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Does a missense mutation underlie defective SOCS4 function in a family with autoimmunity? Context: The aim of this study was to determine the genetic and immunological defects underlying familial manifestations of an autoimmune disorder. 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. 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.
assistant
We present a family with an autoimmune disorder, probably resulting from dysregulated immune responses due to mutations in SOCS4. Final Decision: yes