title: Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).
abstract: Coffin-Lowry syndrome (CLS) is an X-linked disorder characterized by facial dysmorphism, digit abnormalities and severe psychomotor retardation. CLS had previously been mapped to Xp22.2. Recently, mutations in the ribosomal S6 kinase (Rsk-2) gene were shown to be associated with CLS. We have tested five unrelated individuals with CLS for mutations in nine exons of Rsk-2 using Single Strand Conformation Polymorphism (SSCP) analysis. Two patients had the same missense mutation (C340T), which causes an arginine to tryptophan change (R114W). This mutation falls just outside the N-terminal ATP-binding site in a highly conserved region of the protein and may lead to structural changes since tryptophan has an aromatic side chain whereas arginine is a 5 carbon basic amino acid. The third patient also had a missense mutation (G2186A) resulting in an arginine to glutamine change (R729Q). The fourth patient had a 2bp deletion (AG) of bases 451 and 452. This creates a frameshift that results in a stop codon 25 amino acids downstream, thereby producing a truncated protein. This deletion also falls within the highly conserved amino-catalytic domain of the protein. The fifth patient has a nonsense mutation (C2065T) which results in a premature stop codon, thereby producing a truncated protein. These mutations further confirm Rsk-2 as the gene involved in CLS and may help in understanding the structure and function of the protein.
authors: Center for Molecular Studies, JC Self Research Institute for Human Genetics, Greenwood Genetics Center, SC, USA.
authors: F
authors: F
authors: Abidi
authors: S
authors: S
authors: Jacquot
authors: C
authors: C
authors: Lassiter
authors: E
authors: E
authors: Trivier
authors: A
authors: A
authors: Hanauer
authors: C E
authors: CE
authors: Schwartz
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011494:Protein Kinases / Q000235:genetics*; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D013577:Syndrome
chemical_list: D017931:DNA Primers; D004247:DNA; D011494:Protein Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3