PMID- 17412879
OWN - NLM
STAT- MEDLINE
DCOM- 20080306
LR  - 20181113
IS  - 1468-6244 (Electronic)
IS  - 0022-2593 (Print)
IS  - 0022-2593 (Linking)
VI  - 44
IP  - 7
DP  - 2007 Jul
TI  - Myopathy caused by HRAS germline mutations: implications for disturbed myogenic 
      differentiation in the presence of constitutive HRas activation.
PG  - 459-62
AB  - BACKGROUND: Rare reports on patients with congenital myopathy with excess of 
      muscle spindles (CMEMS), hypertrophic cardiomyopathy and variable features 
      resembling Noonan syndrome have been published, but the genetic basis of this 
      condition is so far unknown. METHODS AND RESULTS: We analysed PTPN11 and RAS 
      genes in five unrelated patients with this phenotype, and found HRAS mutations in 
      four of them. Two disease-associated mutations, G12V and G12S, have previously 
      been observed in patients with Costello syndrome (CS), and two other mutations, 
      E63K and Q22K, are novel. All four mutations are predicted to enhance downstream 
      HRas signalling, suggesting that CMEMS is a developmental consequence of 
      sustained HRas activation in skeletal muscle. CONCLUSION: This type of myopathy 
      may represent a previously unrecognized manifestation of CS. However, some 
      patients carrying HRAS mutations may exhibit prominent congenital muscular 
      dysfunction, although features of CS may be less obvious, suggesting that 
      germline HRAS mutations may underlie some cases of otherwise unclassified 
      neonatal neuromuscular disorders.
FAU - van der Burgt, Ineke
AU  - van der Burgt I
FAU - Kupsky, William
AU  - Kupsky W
FAU - Stassou, Stephani
AU  - Stassou S
FAU - Nadroo, Ali
AU  - Nadroo A
FAU - Barroso, Candida
AU  - Barroso C
FAU - Diem, Angelika
AU  - Diem A
FAU - Kratz, Christian P
AU  - Kratz CP
FAU - Dvorsky, Radovan
AU  - Dvorsky R
FAU - Ahmadian, Mohammad Reza
AU  - Ahmadian MR
FAU - Zenker, Martin
AU  - Zenker M
LA  - eng
PT  - Case Reports
PT  - Comparative Study
PT  - Letter
PT  - Research Support, Non-U.S. Gov't
DEP - 20070405
PL  - England
TA  - J Med Genet
JT  - Journal of medical genetics
JID - 2985087R
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Abnormalities, Multiple/*genetics
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Germ-Line Mutation/*genetics
MH  - Humans
MH  - Molecular Sequence Data
MH  - Muscle Spindles/pathology
MH  - Muscular Diseases/*genetics
MH  - Proto-Oncogene Proteins p21(ras)/*genetics
MH  - Sequence Analysis, DNA
MH  - Signal Transduction/genetics
PMC - PMC2598013
COIS- Competing interests: None declared.
EDAT- 2007/04/07 09:00
MHDA- 2008/03/07 09:00
PMCR- 2010/07/01
CRDT- 2007/04/07 09:00
PHST- 2007/04/07 09:00 [pubmed]
PHST- 2008/03/07 09:00 [medline]
PHST- 2007/04/07 09:00 [entrez]
PHST- 2010/07/01 00:00 [pmc-release]
AID - jmg.2007.049270 [pii]
AID - mg49270 [pii]
AID - 10.1136/jmg.2007.049270 [doi]
PST - ppublish
SO  - J Med Genet. 2007 Jul;44(7):459-62. doi: 10.1136/jmg.2007.049270. Epub 2007 Apr 
      5.