http://purl.uniprot.org/citations/26194542 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/26194542 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundKabuki syndrome (KS) is a complex multisystem developmental disorder associated with mutation of genes encoding histone-modifying proteins. In addition to craniofacial, intellectual, and cardiac defects, KS is also characterized by humoral immune deficiency and autoimmune disease, yet no detailed molecular characterization of the KS-associated immune phenotype has been reported.ObjectiveWe sought to characterize the humoral immune defects found in patients with KS with lysine methyltransferase 2D (KMT2D) mutations.MethodsWe comprehensively characterized B-cell function in a cohort (n = 13) of patients with KS (age, 4 months to 27 years).ResultsThree quarters (77%) of the cohort had a detectable heterozygous KMT2D mutation (50% nonsense, 20% splice site, and 30% missense mutations), and 70% of the reported mutations are novel. Among the patients with KMT2D mutations (KMT2D(Mut/+)), hypogammaglobulinemia was detected in all but 1 patient, with IgA deficiency affecting 90% of patients and a deficiency in at least 1 other isoform seen in 40% of patients. Numbers of total memory (CD27(+)) and class-switched memory B cells (IgM(-)) were significantly reduced in patients with KMT2D(Mut/+) mutations compared with numbers in control subjects (P < .001). Patients with KMT2D(Mut/+) mutations also had significantly reduced rates of somatic hypermutation in IgG (P = .003) but not IgA or IgM heavy chain sequences. Impaired terminal differentiation was noted in primary B cells from patients with KMT2D(Mut/+) mutations. Autoimmune pathology was observed in patients with missense mutations affecting the SET domain and its adjacent domains.ConclusionsIn patients with KS, autosomal dominant KMT2D mutations are associated with dysregulation of terminal B-cell differentiation, leading to humoral immune deficiency and, in some cases, autoimmunity. All patients with KS should undergo serial clinical immune evaluations."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jaci.2015.06.002"xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Xie C."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Bernstein J.A."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Hopkin R.J."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Saal H.M."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Burrow T.A."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Bleesing J."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Khandelwal P."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Risma K."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Assa'ad A.H."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Roehrs P.A."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Filipovich L."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Lindsley A.W."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/author | "Shchelochkov O."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/name | "J Allergy Clin Immunol"xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/pages | "179-187.e10"xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/title | "Defects of B-cell terminal differentiation in patients with type-1 Kabuki syndrome."xsd:string |
http://purl.uniprot.org/citations/26194542 | http://purl.uniprot.org/core/volume | "137"xsd:string |
http://purl.uniprot.org/citations/26194542 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26194542 |
http://purl.uniprot.org/citations/26194542 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26194542 |
http://purl.uniprot.org/uniprot/#_A0A2S0X0M0-mappedCitation-26194542 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26194542 |
http://purl.uniprot.org/uniprot/#_O14686-mappedCitation-26194542 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26194542 |