PMID- 10094187
OWN - NLM
STAT- MEDLINE
DCOM- 19990513
LR  - 20091119
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 7
IP  - 1
DP  - 1999 Jan
TI  - Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).
PG  - 20-6
AB  - 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.
FAU - Abidi, F
AU  - Abidi F
AD  - Center for Molecular Studies, JC Self Research Institute for Human Genetics,
      Greenwood Genetics Center, SC, USA.
FAU - Jacquot, S
AU  - Jacquot S
FAU - Lassiter, C
AU  - Lassiter C
FAU - Trivier, E
AU  - Trivier E
FAU - Hanauer, A
AU  - Hanauer A
FAU - Schwartz, C E
AU  - Schwartz CE
LA  - eng
GR  - 2RO1HD26202/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (DNA Primers)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 90kDa, polypeptide 3)
SB  - IM
MH  - Abnormalities, Multiple/*genetics
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - DNA
MH  - DNA Primers
MH  - Female
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Pedigree
MH  - Protein Kinases/*genetics
MH  - *Ribosomal Protein S6 Kinases, 90-kDa
MH  - Syndrome
EDAT- 1999/03/27 00:00
MHDA- 1999/03/27 00:01
CRDT- 1999/03/27 00:00
PHST- 1999/03/27 00:00 [pubmed]
PHST- 1999/03/27 00:01 [medline]
PHST- 1999/03/27 00:00 [entrez]
AID - 10.1038/sj.ejhg.5200231 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 1999 Jan;7(1):20-6. doi: 10.1038/sj.ejhg.5200231.