Human ITCH E3 ubiquitin ligase deficiency causes syndromic multisystem autoimmune disease.
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.
Lohr
Naomi J
NJ
Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado at Denver, Aurora, CO, USA.
Molleston
Jean P
JP
Strauss
Kevin A
KA
Torres-Martinez
Wilfredo
W
Sherman
Eric A
EA
Squires
Robert H
RH
Rider
Nicholas L
NL
Chikwava
Kudakwashe R
KR
Cummings
Oscar W
OW
Morton
D Holmes
DH
Puffenberger
Erik G
EG
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
D012097:Repressor Proteins; D004247:DNA; C432966:ITCH protein, human; D044767:Ubiquitin-Protein Ligases