Proteus Syndrome Research Paper

Using these three articles (or more), you should tell the story of the discovery and developmental function (including the relevant signaling pathway) -

Achondroplasia (ACH) is the most common form of short-limb dwarfism occuring in 1 in 15,000 to 28,000 births and appears to be slightly more prevalent in females, but indiscriminent toward race (1-3). Evidence has been found in Egypt for cases of ACH dating back as far as 4500 B.C. (4). In simplest terms, ACH is a disease where the dwarfing of bones formed in the cartilage occurs (5). There are many features that accompany this disease including rhizomelic (proximal) shortening of the extremities, megalencephaly (enlarged brain), short stature, trident hand, and frontal bossing (prominent forehead) (1, 3, 4, 6-8). Expression of this gene at high levels is primarily found in cells of the nervous system and the cartilage rudiments and

Researchers believe the mutation of this gene causes too much bone to grow instead of muscle.

Hutchinson-Gilford Progeria Syndrome (HGPS) affects approximately 1 in 4-8 million newborns. It is characterized by rapid aging, but no symptoms are seen at birth. Within a year, infected children start showing symptoms such as a receding jaw, pointy nose, partial to total hair loss (alopecia), fat loss, bone disfigurements, a short stature and skin problems (Pollex 2004). The disease progresses with time, and eventually leads to death at an average age of about 13 years. Death is usually caused by some form of cardiovascular disease, usually induced by atherosclerosis (Wuyts et al. 2005). Most cases of HGPS are due to de novo autosomal dominant point mutations in the lamin A/C gene (LMNA). There are some reported cases suggesting autosomal recessive inheritance, but further testing needs to be performed.

and among the 9 offspring of 2 sisters, Rava in1967 found 6 affected. Khalifa in1989 described a

Crouzon syndrome is an autosomal dominant genetic disorder and is the most common craniosynostosis syndrome with an incidence of 16.5/1,000,000, representing 4.8% of craniosynostosis cases, and a prevalence of 1/60,000 in the U.S. Crouzon syndrome is caused by an activating mutation of the FGFR2 gene, an important factor in the conversion of the fibrous joint areas between sutures to bone. Specifically, the missense mutation occurs within exons IIIa and exon IIIc of the extracellular immunoglobulin domain, IgIII, in 95% of Crouzon patients. Generally, cysteine residues are replaced, preventing critical disulfide bond formation and ultimately cause spatiotemporal malformations. There are at least 32 documented unique mutations, 30-60% of which are sporadic, spontaneous mutations.

C-Akt, a serine-threonine kinase is one target of PI39K. C-Akt is the prototypical member of a mammalian Akt isoform family. The regulation to Akt may be phosphorylation or direct binding the Akt pleckstrin homology domain with PI39K lipid products. PI39K-independent Akt stimuli had been identified [3]. AMG 319 inhibited basal AKT phosphorylation and proliferation in lymphoid tumor cells [1].

Fibrodysplasia Ossificans Progressiva disease also known as ‘FOP’ is a rare genetic disease of the connective tissue. FOP can be characterized by malformations of the big toe. This malformation is a characteristic feature that helps distinguish the disease from other muscle and bone issues. It is a disease that is caused by a mutation in the bodies repair mechanism. This causes muscle and connective tissue such as ligaments and tendons, to be ossified spontaneously or when they are damaged. Sometimes the bone can be permanently frozen in place in some cases. FOP is usually seen in early childhood it starts with the neck and shoulder and proceeds down the body and into the limbs. People who suffer from FOP are basically imprisoned by their own skeleton. Majority of FOP cases are sporadic and are a result from a new gene mutation (Lerardi-Curto and Lynne). This mutation is an autosomal dominant disorder; this means it affects those who are heterozygous with a homozygous recessive partner because of this it means their children will have a fifty percent chance of having FOP. Most cases of FOP are a result from new mutations in the gene. People who have FOP and have the heterozygous phenotype have less severe affects than those who have the homozygous dominant phenotype. Patients who have FOB have the ossification gene that is still working in their bodies and it is usually turned off after a

The genetic mutation that I am doing is called Proteus Syndrome. Proteus Syndrome is a highly variable and is named after Greek-god Proteus who could change his shape. Only a few more than 200 cases have been confirmed worldwide with estimates that about 120 people are currently alive with the condition. Those most readily diagnosed are also the most severely disfigured bones, muscles, fatty tissues, and blood and lymphatic vessels. Proteus syndrome is an overgrowth disorder caused by a rare genetic mosaicism.

A biopsy is essential to confirm the diagnosis. On microscopic examination, the tumor demonstrates peculiar features of expohytic papillary growth consisting of atypical cells and fibrovascular core. These atypical squamous epithelial cells showed the characteristics of hyperchromatism, nuclear atypia, cancer pearls, apoptotic bodies, nuclear atypia and individual keratinization. Mild stromal invasion was noticed.

After diagnosing and studying Progeria in children, German scientist, Otto Werner discovered Adult Progeria, which was named after him called, Werner’s Syndrome. Too like Progeria in the children, the same effects but in adults starting as early as the age of twenty-one. Werner’s Syndrome classified by the development of a distinctive high pitch voice, cataracts in both eyes and a number of health problems that stem from the disorder. During teenage years one may not even appear to have symptoms of this particular condition, however by the early twenties, it is more obvious. This disorder has commonly been identified in Japan

The rapid, thorough evaluation is very essential in the evaluation of PA. The management of PA focused on two aspects, endocrinopathy and acute neurologic deficits from tumor mass. Treatment and management includes medical stabilization, administration of high-dose steroids to correct hypocortisolism, electrolyte evaluation, imaging and surgical decompression

The concept of developmental field defects (DFDs) given by Martinez-Frias [59] tries to explain that these associated syndromes may have complex aetiology. It may be that a number of signalling pathways are involved in producing field defects and that too at different timings. The timing could possibly explain the type of phenotype- isolated or syndromic [37].

Kai et al IkB Kinase β (IKBKB) mutations in lymphomas that constitutively activate canonical nuclear factor kB (NFkB) signalling. 2014, J Biol Chem 289(38)26960-72.

Over the past centuries a number of researchers have sought to determine the proper meaning of the Greek word proskynesis. It was the German lexicographer Passow who established the following definition: ‘die Hand an den Mund legen, sie mit einem Kusse gegen einen anderen ausstrecken und diesem dadurch seine Ehrfurcht beziegen’ [1]. A considerable amount of literature has been published on proskynesis, primarily focussing on its occurrence in Arrian’s Anabasis Alexandri, which deals with the refusal of Callisthenes to perform proskynesis in front of Alexander of Macedon [2]. Originally, this Persian court ritual was thought to be the only meaning to which the word