Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers

Hisato Suzuki, Toshiki Takenouchi, Tomoko Uehara, Satoshi Takasago, Satoshi Ihara, Hiroshi Yoshihashi, Kenjiro Kosaki

Research output: Contribution to journalArticle

Abstract

Activation of the RAS pathway through either the activation of genes that accelerate the pathway or the suppression of genes that inhibit the pathway leads to a group of disorders collectively referred to as RASopathies. The key molecules of the RAS pathway are KRAS, HRAS, and NRAS. Mutations in these three RAS homolog genes have been shown to be associated with RASopathies. Recently, two patients with a Noonan syndrome phenotype were shown to carry mutations in the yet another RASopathy gene, MRAS (muscle RAS oncogene homolog). Here, we report a patient with a severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant, which represents a recurrent substitution in RAS homologs in various cancers. The patient's dysmorphic features included relative macrocephaly, a down-slanted palpebral fissure, hypertelorism, a depressed nasal bridge, and low-set ears with thick lobes; these facial features are strongly associated with RASopathy. We confirmed that the MRAS gene represents a causative gene for RASopathy.

Original languageEnglish
JournalAmerican Journal of Medical Genetics, Part A
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Noonan Syndrome
Phenotype
Genes
Neoplasms
Megalencephaly
Hypertelorism
Mutation
Eyelids
Oncogenes
Nose
Transcriptional Activation
Ear
Muscles

Keywords

  • Costello syndrome
  • MRAS
  • Noonan syndrome
  • RAS
  • RASopathy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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title = "Severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant: a recurrent substitution in RAS homologs in various cancers",
abstract = "Activation of the RAS pathway through either the activation of genes that accelerate the pathway or the suppression of genes that inhibit the pathway leads to a group of disorders collectively referred to as RASopathies. The key molecules of the RAS pathway are KRAS, HRAS, and NRAS. Mutations in these three RAS homolog genes have been shown to be associated with RASopathies. Recently, two patients with a Noonan syndrome phenotype were shown to carry mutations in the yet another RASopathy gene, MRAS (muscle RAS oncogene homolog). Here, we report a patient with a severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant, which represents a recurrent substitution in RAS homologs in various cancers. The patient's dysmorphic features included relative macrocephaly, a down-slanted palpebral fissure, hypertelorism, a depressed nasal bridge, and low-set ears with thick lobes; these facial features are strongly associated with RASopathy. We confirmed that the MRAS gene represents a causative gene for RASopathy.",
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T2 - a recurrent substitution in RAS homologs in various cancers

AU - Suzuki, Hisato

AU - Takenouchi, Toshiki

AU - Uehara, Tomoko

AU - Takasago, Satoshi

AU - Ihara, Satoshi

AU - Yoshihashi, Hiroshi

AU - Kosaki, Kenjiro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Activation of the RAS pathway through either the activation of genes that accelerate the pathway or the suppression of genes that inhibit the pathway leads to a group of disorders collectively referred to as RASopathies. The key molecules of the RAS pathway are KRAS, HRAS, and NRAS. Mutations in these three RAS homolog genes have been shown to be associated with RASopathies. Recently, two patients with a Noonan syndrome phenotype were shown to carry mutations in the yet another RASopathy gene, MRAS (muscle RAS oncogene homolog). Here, we report a patient with a severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant, which represents a recurrent substitution in RAS homologs in various cancers. The patient's dysmorphic features included relative macrocephaly, a down-slanted palpebral fissure, hypertelorism, a depressed nasal bridge, and low-set ears with thick lobes; these facial features are strongly associated with RASopathy. We confirmed that the MRAS gene represents a causative gene for RASopathy.

AB - Activation of the RAS pathway through either the activation of genes that accelerate the pathway or the suppression of genes that inhibit the pathway leads to a group of disorders collectively referred to as RASopathies. The key molecules of the RAS pathway are KRAS, HRAS, and NRAS. Mutations in these three RAS homolog genes have been shown to be associated with RASopathies. Recently, two patients with a Noonan syndrome phenotype were shown to carry mutations in the yet another RASopathy gene, MRAS (muscle RAS oncogene homolog). Here, we report a patient with a severe Noonan syndrome phenotype associated with a germline Q71R MRAS variant, which represents a recurrent substitution in RAS homologs in various cancers. The patient's dysmorphic features included relative macrocephaly, a down-slanted palpebral fissure, hypertelorism, a depressed nasal bridge, and low-set ears with thick lobes; these facial features are strongly associated with RASopathy. We confirmed that the MRAS gene represents a causative gene for RASopathy.

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KW - Noonan syndrome

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