title: A novel RAB33B mutation in Smith-McCort dysplasia.
abstract: Smith-McCort dysplasia (SMC) is a rare autosomal recessive spondylo-epi-metaphyseal dysplasia with skeletal features identical to those of Dyggve-Melchior-Clausen syndrome (DMC) but with normal intelligence and no microcephaly. Although both syndromes were shown to result from mutations in the DYM gene, which encodes the Golgi protein DYMECLIN, a few SMC patients remained negative in DYM mutation screening. Recently, autozygosity mapping and exome sequencing in a large SMC family have allowed the identification of a missense mutation in RAB33B, another Golgi protein involved in retrograde transport of Golgi vesicles. Here, we report a novel RAB33B mutation in a second SMC case that leads to a marked reduction of the protein as shown by Western blot and immunofluorescence. These data confirm the genetic heterogeneity of SMC dysplasia and highlight the role of Golgi transport in the pathogenesis of SMC and DMC syndromes.
authors.affiliation: Inserm, U676, Paris, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Dupuis
authors.forename: Sophie
authors.initials: S
authors.lastname: Lebon
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Séverine
authors.initials: S
authors.lastname: Drunat
authors.forename: Luitgard M
authors.initials: LM
authors.lastname: Graul-Neumann
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: Vincent
authors.initials: V
authors.lastname: El Ghouzzi
mesh_terms: D004392:Dwarfism / Q000235:genetics / Q000503:physiopathology; D059472:Exome; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000503:physiopathology; D018740:Genetic Heterogeneity; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000151:congenital / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D017421:Sequence Analysis; D055815:Young Adult; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C477370:DYM protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C486397:RAB33B protein, human; D020691:rab GTP-Binding Proteins