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: Patricia Marques Pereira, Delphine Heron, André Hanauer
• Journal: Human genetics (Hum Genet) Vol. 122 Issue 5 Pg. 541-3 (Dec 2007) ISSN: 1432-1203 [Electronic] Germany
• PMID: 17717706 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Recombinant Proteins
• DNA
• Ribosomal Protein S6 Kinases, 90-kDa
• ribosomal protein S6 kinase, 90kDa, polypeptide 3

Topics

• Amino Acid Sequence
• Base Sequence
• Cell Line
• Coffin-Lowry Syndrome (enzymology, genetics)
• DNA (genetics)
• Exons
• Gene Duplication
• Humans
• Male
• RNA, Messenger (genetics)
• Recombinant Proteins (chemistry, genetics, metabolism)
• Ribosomal Protein S6 Kinases, 90-kDa (chemistry, genetics, metabolism)
• Tandem Repeat Sequences