title: The first large duplication of the RSK2 gene identified in a Coffin-Lowry syndrome patient.
abstract: Heterogeneous mutations in the X-linked gene RPS6KA3, encoding the protein kinase RSK2, are responsible for Coffin-Lowry Syndrome. Here we have further studied a male patient with a highly suggestive clinical diagnosis of CLS but in whom no mutation was found by exon sequencing. Western blot analysis revealed a protein much larger than the normal expected size. Sequencing of the RSK2 cDNA, showed the presence of an in-frame tandem duplication of exons 17-20. The mutated RSK2 protein was found to be inactive in an in-vitro kinase assay. This event, which was the result of a homologous unequal recombination between Alu sequences, is the first reported large duplication of the RPS6KA3 gene. Our finding provides further evidence that immunoblot analysis, or a molecular assay capable to detect large genomic mutational events, is essential for patients with a highly suggestive CLS clinical diagnosis but remaining without mutation after exon sequencing.
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P. 10142, 67404, Illkirch Cedex, C.U. de Strasbourg, France.
authors: Patricia
authors: P
authors: Marques Pereira
authors: Delphine
authors: D
authors: Heron
authors: André
authors: A
authors: Hanauer
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D038921:Coffin-Lowry Syndrome / Q000201:enzymology / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005091:Exons; D020440:Gene Duplication; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020080:Tandem Repeat Sequences
chemical_list: D012333:RNA, Messenger; D011994:Recombinant Proteins; D004247:DNA; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3
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