https://padlet.com/nth001/lt3w3138nqxtub0k en-us 2021-03-16 14:42:53 UTC 2021-03-22 16:07:01 UTC hello@padlet.com nth001 https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316110382 Heart Defects in Costello Syndrome involving the HRAS gene on chromosome 11. ]]> 2021-03-16 15:01:56 UTC https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316110382 nth001 https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316133190 The HRAS gene is apart of a family of oncogenes, which are genes that are mainly involved in cell signaling. The HRAS functions through a process called signal transduction when it relays a signal from outside of the cell, into the cell's nucleus. The signal helps the cell to grow and divide properly so that cells can differentiate into their effective functions and uses within a human. The H-Ras protein itself is a GTPase because it coverts GTP into GDP or vise versa when it is phosphorylated or dephosphorylated, depending on the cell signaling. ]]> 2021-03-16 15:05:39 UTC https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316133190 nth001 https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316244787 -Short stature 
-Craniofacial abnormalities such as prominent forehead, short nose, and full cheeks and lips 
-Musculoskeletal defects such as limited range of motion at the elbows, broad fingers, and tight tendons in the feet. 
-One of the most debilitating symptoms is heart defects. Heart defects that present in patients with Costello Syndrome vary. Structural abnormalities, cardiomyopathy, and dysrhythmias due to an increase in cell division caused by the mutation. ]]> 2021-03-16 15:23:33 UTC https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316244787 nth001 https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316638699 At nucleotide 34 in codon 12 of the HRAS gene on chromosome 11, there is an adenine base substituted in the position where a guanine base resides in the wild type gene.  ]]> 2021-03-16 16:28:17 UTC https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316638699 nth001 https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316671005 HRAS Gene. MedLine Plus . [accessed 2021 Feb 20]. https://medlineplus.gov/genetics/gene/hras/

Gripp, Karen W et al. “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.” American journal of medical genetics. [Accessed 2021 Mar 16] Part A vol. 158A,9 (2012): 2106-18. doi:10.1002/ajmg.a.35449

Estep, Anne L., et al. “HRAS Mutations In Costello Syndrome: Detection of Constitutional Activating Mutations in CODON 12 and 13 and Loss of Wild-Type Allele in malignancy.” American Journal of Medical Genetics [Accessed 2021 Mar 16] Part A, vol. 140A, no. 1, 2005, pp. 8–16., doi:10.1002/ajmg.a.31078. 







]]> 2021-03-16 16:33:54 UTC https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316671005 nth001 https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316690478  Wild Type DNA Sequence 
5'-GCCGGCGGT-3'
Wild Type RNA Sequence: 
3'-CGGCCGCCA-5'

Mutant DNA Sequence: 
5'-GCCAGCGGT-3'
Mutant RNA Sequence: 
3'-CGGUCGCCA-5' 
As seen above the mRNA sequence would change form a C to a U at nucleotide 34. ]]> 2021-03-16 16:37:22 UTC https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316690478 nth001 https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316969755 The translational effects are as follows in Costello Syndrome in codons 11 through 13 with codon 12, G to A base substitution that constitutes the most common mutation seen. 

Codon 11        Codon 12       Codon 13 
      Ala                  Ser                  Gly 

The change in the protein structure will enable the HRAS protein to be phosphorylated more easily because the glycine residue does not have a hydroxyl group like serine. Hydroxyl groups can be readily phosphorylated and this change in a GTPase can result in the protein constantly being turned on due to prolonged phosphorylation, thus unregulated cell growth may occur. ]]> 2021-03-16 17:24:59 UTC https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1316969755 nth001 https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1317042633 As stated in previously boxes, the HRAS gene belongs to a family of oncogenes that is a key regulator for cell growth and division in humans. Since the HRAS gene is a GTPase, it converts GTP into GDP and vise versa via phosphorylation and dephosphorylating turning the GTPase on when GTP (phosphorylated) is bound and off when GDP (dephosphorylated) is bound. When a serine residue is translated in the mutated protein this allows phosphorylation to have extensive effects by disabling the hydrolytic activity of the GTPase, which keeps it phosphorylated. As a result, signaling effects of the HRAS protein are increased and can become unregulated. This manifests in several heart conditions such as cardiomyopathy which is the thickening of the heart walls due to unregulated cell growth in the myocardium. Dysrhythmias can also occur because the heart may have to work harder to pump enough oxygenated blood throughout the body as well as recycle unoxygenated blood as it returns to the heart from the lungs if cardiac cells are rapidly dividing. In all, the unregulated cell growth that occurs when the HRAS gene is effected can be detrimental to the child effected and leave long lasting heart defects and may result in various cancers throughout the body if not treated properly.  ]]> 2021-03-16 17:37:42 UTC https://padlet.com/nth001/lt3w3138nqxtub0k/wish/1317042633