title: UFD1L, a developmentally expressed ubiquitination gene, is deleted in CATCH 22 syndrome.
abstract: The CATCH 22 acronym outlines the main clinical features of 22q11.2 deletions (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcemia), usually found in DiGeorge (DGS) and velo-cardio-facial (VCFS) syndromes. Hemizygosity of this region may also be the cause of over 100 different clinical signs. The CATCH 22 locus maps within a 1.5 Mb region, which encompasses several genes. However, no single defect in 22q11.2 hemizygous patients can be ascribed to any gene so far isolated from the critical region of deletion. We have identified a gene in the CATCH 22 critical region, whose functional features and tissue-specific expression suggest a distinct role in embryogenesis. This gene, UFD1L, encodes the human homolog of the yeast ubiquitin fusion degradation 1 protein (UFD1p), involved in the degradation of ubiquitin fusion proteins. Cloning and characterization of the murine homolog (Ufd1l) showed it to be expressed during embryogenesis in the eyes and in the linear ear primordia. These data suggest that the proteolytic pathway that recognizes ubiquitin fusion proteins for degradation is conserved in vertebrates and that the UFD1L gene hemizygosity is the cause of some of the CATCH 22-associated developmental defects.
authors.affiliation: Istituto di Neurologia, Università di Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pizzuti
authors.forename: G
authors.initials: G
authors.lastname: Novelli
authors.forename: A
authors.initials: A
authors.lastname: Ratti
authors.forename: F
authors.initials: F
authors.lastname: Amati
authors.forename: A
authors.initials: A
authors.lastname: Mari
authors.forename: G
authors.initials: G
authors.lastname: Calabrese
authors.forename: S
authors.initials: S
authors.lastname: Nicolis
authors.forename: V
authors.initials: V
authors.lastname: Silani
authors.forename: B
authors.initials: B
authors.lastname: Marino
authors.forename: G
authors.initials: G
authors.lastname: Scarlato
authors.forename: S
authors.initials: S
authors.lastname: Ottolenghi
authors.forename: B
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002869:Chromosome Aberrations / Q000196:embryology / Q000235:genetics*; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D018076:DNA, Complementary; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C491497:UFD1 protein, human; D014452:Ubiquitins; C107396:Ufd1 protein, mouse