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A Novel RAB33B Mutation in S mith– M c C ort Dysplasia
Author(s) -
Dupuis Nina,
Lebon Sophie,
Kumar Manoj,
Drunat Séverine,
GraulNeumann Luitgard M.,
Gressens Pierre,
El Ghouzzi Vincent
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22235
Subject(s) - missense mutation , biology , golgi apparatus , mutation , exome sequencing , genetics , dysplasia , exome , gene , endoplasmic reticulum
S mith– M c C ort dysplasia ( SMC ) is a rare autosomal recessive spondylo‐epi‐metaphyseal dysplasia with skeletal features identical to those of D yggve– M elchior– C lausen 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 G olgi 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 G olgi protein involved in retrograde transport of G olgi 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 W estern blot and immunofluorescence. These data confirm the genetic heterogeneity of SMC dysplasia and highlight the role of G olgi transport in the pathogenesis of SMC and DMC syndromes.