Costello syndrome is an extremely rare genetic disorder with growth delay after birth and typically results in short stature during childhood. It is one of the RASopathy of Ras/MAPK pathway syndromes. It affects the t...Costello syndrome is an extremely rare genetic disorder with growth delay after birth and typically results in short stature during childhood. It is one of the RASopathy of Ras/MAPK pathway syndromes. It affects the transforming protein p<sup>21</sup>, an enzyme that in humans is encoded by the HRAS gene. H-Ras is a small G protein and once bound to Guanosine triphosphate, it will activate a Raf kinase like C-Raf, the next step in the MAPK/ERK pathway (mitogen-actvated protein kinase/extracellular signal-regulated kinase) i.e., MEK (mitogen-actvated ERK kinase), a protein that phosphorylate ERK which can directly and indirectly activate many transcription factors. This pathway is also known as Ras-Raf, MEK-ERK pathway, which is a chain of proteins on the cell that communicate a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Activation of ERK 1/2 is involved in signal transduction pathways associated with cardiac hypertrophy. The developmental syndromes caused by germline mutations in genes that alter the RAS components of the MAP/ERK signal transduction pathway are called “RASopathies”. Cardiovascular abnormalities are important features of Costello syndrome and other RASopathies such as Noonan syndrome. Background of this case report described the congenital valvular pulmonic stenosis and ventriculomegaly associated with Costello syndrome by transthoracic echocardiographic imaging in a 9-year-old male boy.展开更多
RASopathies是一组由于Ras/丝裂原激活蛋白激酶(Ras/mitogen activated protein kinase,MAPK)通路中的组分或调节因子的编码基因发生突变引起的一系列疾病。Ras/MAPK通路在调控细胞发育过程中发挥重要作用,因此RASopathies涉及疾病众多...RASopathies是一组由于Ras/丝裂原激活蛋白激酶(Ras/mitogen activated protein kinase,MAPK)通路中的组分或调节因子的编码基因发生突变引起的一系列疾病。Ras/MAPK通路在调控细胞发育过程中发挥重要作用,因此RASopathies涉及疾病众多,且临床表现相互重叠,诊断难度大。其中,矮小症是RASopathies最常见的临床表现之一,但导致矮小症的机制有待进一步探索,且生长激素治疗RASopathies的效果差异较大。本文就RASopathies及其在矮小症中的研究进展作一综述。展开更多
文摘Costello syndrome is an extremely rare genetic disorder with growth delay after birth and typically results in short stature during childhood. It is one of the RASopathy of Ras/MAPK pathway syndromes. It affects the transforming protein p<sup>21</sup>, an enzyme that in humans is encoded by the HRAS gene. H-Ras is a small G protein and once bound to Guanosine triphosphate, it will activate a Raf kinase like C-Raf, the next step in the MAPK/ERK pathway (mitogen-actvated protein kinase/extracellular signal-regulated kinase) i.e., MEK (mitogen-actvated ERK kinase), a protein that phosphorylate ERK which can directly and indirectly activate many transcription factors. This pathway is also known as Ras-Raf, MEK-ERK pathway, which is a chain of proteins on the cell that communicate a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Activation of ERK 1/2 is involved in signal transduction pathways associated with cardiac hypertrophy. The developmental syndromes caused by germline mutations in genes that alter the RAS components of the MAP/ERK signal transduction pathway are called “RASopathies”. Cardiovascular abnormalities are important features of Costello syndrome and other RASopathies such as Noonan syndrome. Background of this case report described the congenital valvular pulmonic stenosis and ventriculomegaly associated with Costello syndrome by transthoracic echocardiographic imaging in a 9-year-old male boy.
文摘RASopathies是一组由于Ras/丝裂原激活蛋白激酶(Ras/mitogen activated protein kinase,MAPK)通路中的组分或调节因子的编码基因发生突变引起的一系列疾病。Ras/MAPK通路在调控细胞发育过程中发挥重要作用,因此RASopathies涉及疾病众多,且临床表现相互重叠,诊断难度大。其中,矮小症是RASopathies最常见的临床表现之一,但导致矮小症的机制有待进一步探索,且生长激素治疗RASopathies的效果差异较大。本文就RASopathies及其在矮小症中的研究进展作一综述。
