Nf1's Pathogenesis Essay

Neurofibromatosis is a disorder affecting the chromosomes of the human body. It is a hereditary disorder affecting the nervous system. The term neurofibromatosis actually refers to two different genetic diseases. The most common type is NF 1, and the less common type is NF 2. Both disorders are transmitted in an autosomal dominant fashion. An autosomal dominant disease is a disorder caused by the presence of a single autosomal dominant gene; an abnormal factor located on any chromosome other than the sex chromosome. They are both characterized by occurrences in multiple neurofibromas.

At an almost ironically small 1500 grams (3.3 pounds) the human brain is considered the “command center” of the human intelligence. With the help of the branching nerves, the brain has ability to interpret senses, to achieve the movement of the body and act as regulator of all behaviors; and that’s just a small fraction of the nervous systems responsibilities. As the Nervous System, the brain and nerves work in close association with the rest of our body systems to generate the hundreds of thousands of basic steps needed for life. In this multifaceted body system, any seemingly trivial error can lead to catastrophic alteration to the machine that is the human body. We are constantly achieving understanding of the mechanisms of diseases and syndromes and somehow there is still, simultaneously, an abundance of new pathologies that science has yet begun to understand. One such disease that affects the nervous system specifically is Schwannomatosis. In this paper, we will discuss the symptoms, platforms of the disease, complications, some treatment options and outcomes.

Emanuel Syndrome is a congenital chromosomal disorder that can disrupt the development of multiple parts of the entire body. Though numbers are growing, in 2012, over 200 causes of Emanuel Syndrome have been reported in the United States (Zaki, Mohamed, Kamel, El-Gerzway & El-Ruby, 2012). The numbers of those diagnosed with this disorder are low due to the low incidence of this population, but also because of how new this disorder is. In 2004, Emanuel Syndrome officially got its name (Chromosome 22 Central, 2016). Before this time, individuals who had symptoms of this disorder were diagnosed with varying names such as, Cat Eye Syndrome, 22 Syndrome, or 22q11.2 Deletion Syndrome. In 2004, a support parent group for children with these

Jorde, L. B., Bamshad, M. J., White, R. L. and John C. Carey MD MPH Dr. (2006) Medical genetics updated edition for 2006 – 2007. 3rd edn. United States: Mosby.

From Cystic Fibrosis to Down’s Syndrome and Sickle Cell Anemia, there are tens of thousands of genetic disorders, with many more to be discovered. The fascinating thing about genetic disorders is that when we were born it’s a gamble whether or not we would come into this world with a genetic disorder. Although genetic disorders are quite rare and we take being born without one as granted, there are many out there that live with these disorders everyday. My research paper will focus on the specificalities of a few genetic disorders, the disorders presented in my paper are Marfan Syndrome, Hutchinson-Gilford Progeria, Cystic Fibrosis, and Sickle Cell Anemia. My paper will encompass important specifics

There was a ratio of 4:1 male-to female for the development of the disease. Important to note was that it was reported that the authors cannot give any real explanation for the male preponderance. More specifically, genetic analysis showed the patient to be heterozygous and have a single-nucleotide mutation at codon 41A>G. This mutation resulted the amino acid asparagine to be switched out with serine. Furthermore, according to a few prediction programs noted within the article it was shown that this substitution of serine could prove damaging. In more detail, the aberrant splicing mentioned before was shown to cause an 8 base pair long deletion within the shwachman-diamond-bodian syndrome gene.

An initial step to investigate the existence of a genetic or hereditary component of a disease is the demonstration of familiarity. These studies are used to design an epidemiological case-control. Thus it appears on one hand the frequency or prevalence of the disease in relatives of carriers of the disorder, and on the other hand there is the frequency of that disorder in relatives of healthy individuals,

“I do not foresee a role anytime soon for investigating the genotype of a particular child in order to help make treatment decisions. I would certainly not advise parents to waste any time or money obtaining any of the ‘genetic scans’ that have become popular lately. They are of no practical help.”(p.22)

Between 750,000 and 1.5 million individuals in the United States have Parkinson's ailment. Most instances of the condition result from an unpredictable connection of ecological and hereditary components. Caucasian men are 1.5 times more probable than ladies to build up the condition, and its prevalence increments with age. Roughly 5 percent of individuals determined to have PD have a family history of the confusion. Such familial cases can be caused by transformations in five qualities that give critical data about atomic pathways associated with the infection. Changes of the LLRK2, or SNCA quality, in an autosomal predominant example. This implies one duplicate of an adjusted quality in every cell is adequate to cause the confusion. In these

In 2010, Francis S. Collins penned The Language of Life: DNA and the Revolution in Personalized Medicine. At that time, he was the director of the Human Genome Project and now currently serves as the head of the National Institutes of Health. Collins is an American geneticist who was influential in discovering the genes responsible for cystic fibrosis and type II diabetes. The Language of Life: DNA and the Revolution in Personalized Medicine begins with a rough overview of genetic principles that will be used in further chapters. The book delves into dominant and recessive genes, single nucleotide polymorphisms (SNPs) and other genetic mutations, as well as, various conditions that arise from the previous genetic circumstances.

In 1993 NF was classified to be a suppressor gene, NF diagnosis had been mapped out into major and minor symptoms and even that NF was linked to behavioral issues and finally in 1990 they found that on the p16 (a tumor suppressor gene) was linked to the development of Malignant tumors. Even in the past 17 years NF research has found that NF1 is linked to various learning difficulties such as ADHD in 2002, In the same year it was found that around 8-13% of NF patients have the probability to develop a MPNST, then later it was found that this type of cancer was related to a mutation within NF and microdeletions. In 2004, it was found that there was a relationship to bone abnormalities and NF creates another possible symptom and diagnostic criteria of NF, and later in 2006 researchers looked into how NF impacted people emotionally and it was found that depending on severity that it can negatively affect a person and their quality of life. (Antonio, J., Goloni-Bertollo, E., & Trídico, L.. Neurofibromatosis: chronological history and current issues.

Neurofibromatosis type 1 (NF1) is the most prevalent inherited disease that predisposes cells to be tumorigenic. Disruption of the NF1 gene abolishes the encoded protein neurofibromin that normally converts active Ras-GTP to inactive Ras-GDP, leading to hyperactive Ras signaling and tumorigenesis. To date the NF1 pathogenesis still remains unclear and no effective drugs have been developed for routine clinical treatment. Human induced pluripotent stem (iPS) cells derived from NF1 patients harboring distinct mutations hold great promise for multiple purposes related to drug testing, understanding disease mechanisms and strengthening the skills critical for patient treatment. The clustered regularly interspaced short palindromic repeats

Our statistical data showed that the ages of the patient group ranged from 5.5 to 12.5 years with a mean of 8.84 ± 2.3 and ages of the children at onset of the disease ranged from 2 to 11.5 years with a mean of 7.36 ± 2.85 and this group included 17 males (56.7%) and 13 females

It occurs due to a lethal autosomal dominant gene of a genetic mosaicism. Their studies showed that RASopathy mutations were activated in the HRAS or KRAS genes which in return activated the RAF-MEK-ERK signaling pathways. These pathways control cell proliferation, survival and differentiation (Levinsohn, Tian and Boyden 2013). This increased cellular proliferation which is why linear nevus sebaceous syndrome is linked most commonly to the HRAS and KRAS genes. The studies of Levinsohn, Tian and Boyden (2013) showed that the mutations of these genes begins during the development of the fetus which is why only 0.3% of infants are born with the lesions. To determine the exact cause of LNSS Wang, Qian and Wu (2015) used an Ion Torrent Personal Genome Machine to target next-generation sequencing. This is designed to translate chemically encoded information such as the bases of DNA and construct a library based on the information received. A long range PCR of the HRAS and KRAS genes was also used and the results showed a missense mutation in mainly the KRAS gene, more specifically in exon 1 which showed an amino acid substitution. On the other hand, Happle (2013) and Groesser, Herschberger and Ruetten (2011) used Sanger sequencing and a snapshot multiplex assay of RAS and found mutations of HRAS and KRAS in 97% of the sebaceous nevi. Their studies also showed that 95% of the lesions were produced from mutations involving the HRAS gene and only 5% were produced from the KRAS gene. A deep tumor analysis of these mutations proposed that the HRAS was exclusively found in the lesioned skin while the KRAS gene was found only in the lesional tissue. Another study done by Levinsohn, Tian and Boyden (2013) included five separate cases of LNSS and an Exome sequence was performed of their paired DNA. Their conclusions were just like those

This disorder is the rarest of the three according to Medical News Today only 15% of the people who inherited neurofibromatosis have this type and some estimated 1 in 40,000 people get it. Schwannomatosis can cause intense pain anywhere in the body as a result of tumors (called schwannomas) that can develop on the cranial, spinal and peripheral nerves. For some people that’s there only symptom. (Mayo Clinic, 2013) Like NF1 and NF2 symptoms and severity varies from person to person. Beside pain, some people may develop tingling, numbness, weakness in the fingers and toes.(Ninds. Nih, 2015) Unlike NF2 people with this type do not develop tumors in the inner ears and do not go deaf. This disease usually affected people in the late stage of life but, prior to late 20s or 30s. (Mayo clinic, 2013) According to (NF Midwest) schwannomatosis was recently recognized that the reason why there is very little information to the causes and treatment for the disorder. Researcher have identified the disorder with” mutation of the SMARCB1 gene located on chromosome 22;” as one of the genes that can cause schwannomatosis. Therefore, it may be inherited or cause by gene mutation. (Mayo Clinic, 2013) As far as diagnosis, genetic testing is done on individual that might have this type of NF and also, if “two or more schwannomas with at least one that has been shown to be a schwannoma on a pathology report.”(nfmidwest, 2012) Treatment