title: Human ITCH E3 ubiquitin ligase deficiency causes syndromic multisystem autoimmune disease.
abstract: Ubiquitin ligases play an important role in the regulation of the immune system. Absence of Itch E3 ubiquitin ligase in mice has been shown to cause severe autoimmune disease. Using autozygosity mapping in a large Amish kindred, we identified a linkage region on chromosome 20 and selected candidate genes for screening. We describe, in ten patients, identification of a mutation resulting in truncation of ITCH. These patients represent the first reported human phenotype associated with ITCH deficiency. These patients not only have multisystem autoimmune disease but also display morphologic and developmental abnormalities. This disorder underscores the importance of ITCH ubiquitin ligase in many cellular processes.
authors.affiliation: Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado at Denver, Aurora, CO, USA.
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Lohr
authors.forename: Jean P
authors.initials: JP
authors.lastname: Molleston
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Strauss
authors.forename: Wilfredo
authors.initials: W
authors.lastname: Torres-Martinez
authors.forename: Eric A
authors.initials: EA
authors.lastname: Sherman
authors.forename: Robert H
authors.initials: RH
authors.lastname: Squires
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Rider
authors.forename: Kudakwashe R
authors.initials: KR
authors.lastname: Chikwava
authors.forename: Oscar W
authors.initials: OW
authors.lastname: Cummings
authors.forename: D Holmes
authors.initials: DH
authors.lastname: Morton
authors.forename: Erik G
authors.initials: EG
authors.lastname: Puffenberger
mesh_terms: D000595:Amino Acid Sequence; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D003241:Consanguinity; D004247:DNA / Q000235:genetics; D002658:Developmental Disabilities / Q000201:enzymology / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010375:Pedigree; D010641:Phenotype; D012097:Repressor Proteins / Q000172:deficiency* / Q000235:genetics*; D013577:Syndrome; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency* / Q000235:genetics*; D014481:United States; D055815:Young Adult
chemical_list: D012097:Repressor Proteins; D004247:DNA; C432966:ITCH protein, human; D044767:Ubiquitin-Protein Ligases