title: Hemizygosity for the COP9 signalosome subunit gene, SGN3, in the Smith-Magenis syndrome.
abstract: Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with an interstitial deletion of chromosome band 17p11.2. The critical region is extremely gene-rich and spans approximately 1.5-2.0 Mb of DNA. Here we report the localization and partial characterization of the gene for subunit 3 of the COP9 signalosome, SGN3. SGN3 maps to the distal portion of the SMS critical interval, between SREBF1 and cCI17-638. We assessed the potential effect of haploinsufficiency of SGN3 in SMS patient lymphoblastoid cell lines through transfection studies and western analysis. Our results indicate that the COP9 signalosome assembles properly in these cells and appears to have normal expression and a kinase function intact. However, because the role of the COP9 signalosome in embryogenesis or differentiation is still uncertain, we cannot rule out the involvement of this gene in the Smith-Magenis syndrome.
authors.affiliation: Department of Zoology, Michigan State University, East Lansing, Michigan, USA. elsea@pilot.msu.edu
authors.forename: S H
authors.initials: SH
authors.lastname: Elsea
authors.forename: K
authors.initials: K
authors.lastname: Mykytyn
authors.forename: K
authors.initials: K
authors.lastname: Ferrell
authors.forename: K L
authors.initials: KL
authors.lastname: Coulter
authors.forename: P
authors.initials: P
authors.lastname: Das
authors.forename: W
authors.initials: W
authors.lastname: Dubiel
authors.forename: P I
authors.initials: PI
authors.lastname: Patel
authors.forename: J E
authors.initials: JE
authors.lastname: Metherall
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D000075686:COP9 Signalosome Complex; D002478:Cells, Cultured; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D006224:Cricetinae; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D006822:Hybrid Cells; D008607:Intellectual Disability / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D011494:Protein Kinases / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013577:Syndrome
chemical_list: D016328:NF-kappa B; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D004247:DNA; D008156:Luciferases; D011494:Protein Kinases; D000075686:COP9 Signalosome Complex