{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gripp KW"],"funding":["NIGMS NIH HHS"],"pagination":["2106-18"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4166655"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["158A(9)"],"pubmed_abstract":["Costello syndrome is caused by HRAS germline mutations affecting Gly(12) or Gly(13) in >90% of cases and these are associated with a relatively homogeneous phenotype. Rarer mutations in other HRAS codons were reported in patients with an attenuated or mild phenotype. Disease-associated HRAS missense mutations result in constitutive HRAS activation and increased RAF-MEK-ERK and PI3K-AKT signal flow. Here we report on a novel heterozygous HRAS germline alteration, c.266C>G (p.S89C), in a girl presenting with severe fetal hydrops and pleural effusion, followed by a more benign postnatal course. A sibling with the same mutation and fetal polyhydramnios showed a Dandy-Walker malformation; his postnatal course was complicated by severe feeding difficulties. Their apparently asymptomatic father i"],"journal":["American journal of medical genetics. Part A"],"pubmed_title":["A novel HRAS substitution (c.266C>G; p.S89C) resulting in decreased downstream signaling suggests a new dimension of RAS pathway dysregulation in human development."],"pmcid":["PMC4166655"],"funding_grant_id":["8P20GM103464","P20 GM103446","P20 GM103464"],"pubmed_authors":["Stabley DL","Rosenberger G","Sol-Church K","Gripp KW","Hopkins E","Meien S","Vinette K","Bifeld E"],"additional_accession":[]},"is_claimable":false,"name":"A novel HRAS substitution (c.266C>G; p.S89C) resulting in decreased downstream signaling suggests a new dimension of RAS pathway dysregulation in human development.","description":"Costello syndrome is caused by HRAS germline mutations affecting Gly(12) or Gly(13) in >90% of cases and these are associated with a relatively homogeneous phenotype. Rarer mutations in other HRAS codons were reported in patients with an attenuated or mild phenotype. Disease-associated HRAS missense mutations result in constitutive HRAS activation and increased RAF-MEK-ERK and PI3K-AKT signal flow. Here we report on a novel heterozygous HRAS germline alteration, c.266C>G (p.S89C), in a girl presenting with severe fetal hydrops and pleural effusion, followed by a more benign postnatal course. A sibling with the same mutation and fetal polyhydramnios showed a Dandy-Walker malformation; his postnatal course was complicated by severe feeding difficulties. Their apparently asymptomatic father i","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Sep","modification":"2026-04-29T16:56:32.648Z","creation":"2019-03-27T01:35:50Z"},"accession":"S-EPMC4166655","cross_references":{"pubmed":["22821884"],"doi":["10.1002/ajmg.a.35449"]}}