{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:33:38Z","timestamp":1762673618452,"version":"build-2065373602"},"reference-count":28,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> 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.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods and results:<\/jats:bold> We analysed <jats:italic>PTPN11<\/jats:italic> and <jats:italic>RAS<\/jats:italic> genes in five unrelated patients with this phenotype, and found <jats:italic>HRAS<\/jats:italic> 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.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion:<\/jats:bold> This type of myopathy may represent a previously unrecogned manifestation of CS. However, some patients carrying <jats:italic>HRAS<\/jats:italic> mutations may exhibit prominent congenital muscular dysfunction, although features of CS may be less obvious, suggesting that germline <jats:italic>HRAS<\/jats:italic> mutations may underlie some cases of otherwise unclassified neonatal neuromuscular disorders.<\/jats:p>","DOI":"10.1136\/jmg.2007.049270","type":"journal-article","created":{"date-parts":[[2007,4,5]],"date-time":"2007-04-05T21:00:11Z","timestamp":1175806811000},"page":"459-462","source":"Crossref","is-referenced-by-count":76,"title":["Myopathy caused by <i>HRAS<\/i> germline mutations: implications for disturbed myogenic differentiation in the presence of constitutive HRas activation"],"prefix":"10.1136","volume":"44","author":[{"given":"Ineke","family":"van der 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