| http://purl.uniprot.org/citations/26783323 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26783323 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26783323 | http://www.w3.org/2000/01/rdf-schema#comment | "A brother and sister developed a previously undescribed constellation of autoimmune manifestations within their first year of life, with uncontrollable bullous pemphigoid, colitis, and proteinuria. The boy had hemophilia due to a factor VIII autoantibody and nephrotic syndrome. Both children required allogeneic hematopoietic cell transplantation (HCT), which resolved their autoimmunity. The early onset, severity, and distinctive findings suggested a single gene disorder underlying the phenotype. Whole-exome sequencing performed on five family members revealed the affected siblings to be compound heterozygous for two unique missense mutations in the 70-kD T cell receptor ζ-chain associated protein (ZAP-70). Healthy relatives were heterozygous mutation carriers. Although pre-HCT patient T cells were not available, mutation effects were determined using transfected cell lines and peripheral blood from carriers and controls. Mutation R192W in the C-SH2 domain exhibited reduced binding to phosphorylated ζ-chain, whereas mutation R360P in the N lobe of the catalytic domain disrupted an autoinhibitory mechanism, producing a weakly hyperactive ZAP-70 protein. Although human ZAP-70 deficiency can have dysregulated T cells, and autoreactive mouse thymocytes with weak Zap-70 signaling can escape tolerance, our patients' combination of hypomorphic and activating mutations suggested a new disease mechanism and produced previously undescribed human ZAP-70-associated autoimmune disease."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.org/dc/terms/identifier | "doi:10.1084/jem.20150888"xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.org/dc/terms/identifier | "doi:10.1084/jem.20150888"xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Brenner S.E."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Brenner S.E."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Kuriyan J."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Kuriyan J."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Olson J.L."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Olson J.L."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Weiss A."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Weiss A."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Srinivasan R."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Srinivasan R."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Cowan M.J."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Cowan M.J."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Puck J.M."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Puck J.M."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Punwani D."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Punwani D."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Fu S.M."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Fu S.M."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Chan A.Y."xsd:string |
| http://purl.uniprot.org/citations/26783323 | http://purl.uniprot.org/core/author | "Chan A.Y."xsd:string |