Rett Syndrome Analysis

Microglia are resident immune cells in the CNS, separated from many blood-borne molecules by the BBB. However, evidence suggests that BBB endothelial cells either act as transporters of hormones and cytokines across the BBB or as classic receptor sites, possibly reacting to signals in the blood by secreting other signals into the CNS.8 By these mechanisms, microglia can become activated in response to inflammatory stimulation such as the cytokines and hormones that cross the BBB.9 Also, metabolic disease frequently leads to compromise of the BBB, providing greater access for circulating molecules to the CNS. It is not clear whether metabolic disease causes microglia to weaken the BBB, or whether the BBB is weakened first, with microglia then

Cri-du-Chat (cat’s cry) Syndrome is a rare chromosomal disorder that is caused by the deletion of genetic material on chromosome 5. Due to this, this syndrome has an alternative name, known as 5p-, or 5p minus syndrome. Although this genetic defect is able to be diagnosed, the cause of the deletion on the chromosome is unknown. Almost all cases of the Cri-du-Chat Syndrome are found to have no relation with family members or previous generations. This syndrome is generally not inherited, as the deletion occurs randomly during meiosis (the formation of the gametes). In about 90% of people who have this condition, the deletion is completely random and is not inherited. The remaining 10% of affected people inherit a chromosome with a deleted section from an unaffected parent. This is because the parents’ balanced

Five other gene disorder that contributes to autism are (1) "EN2 (Engrailed 2) involved in cerebellum development. (2) GABR (Gamma Amino Butyric Acid Receptor) regulates brain cell migration. (3) OXTR (Oxytocin Receptor) participating in the response to stress and social skills. (4) RELN (Reelin) involved in neuronal migration in the developing brain. (5) SLC6A4, a serotonin transporter gene” (Johnson, Giarelli, Lewis, & Rice, 2013). As a result of all the researches done several chromosomal loci have been shown to be linked to Autistic Spectrum disorder including those at 2q24-2q31, 7q22-7q31, 7q34-7q36, and 17q11-17q21. Structural chromosomal changes involving deletions and duplication at 7q11, 15q11-15q13, 17p11.2, 22q11.2, and 22q13 have also been associated with forms of autism. However, the most common chromosomal abnormalities currently associated with autism include the fragile X mutation, other sex chromosome abnormalities, and abnormalities of 15q11-q13. “Evidence has shown that duplications of 15q11–q13 have led to higher risks of Autism Spectrum Disorder and developmental and cognitive deficits” (Flashner, Russo, Boileau, Leong, & Gallicano, 2013). Chromosome 15q11-q13.1 region is subject to genomic imprinting, which is an epigenetic process that results in monoallelic gene expression. Duplications lead to autism and are usually maternal in origin. Deletion of the maternal allele of chromosome 15q11-q13 cause Angelman syndrome (AS) a neurodevelopmental disorder

All forms of CMT1 are autosomal dominant. This means that it is unrelated to sex and is typically passed from one generation to the next without skipping. These varieties of CMT have to be passed down from a parent afflicted by the ailment. An unaffected carrier cannot exist. Because of this, and depending on the genetic makeup of the parents, the chances of having a child with CMT are 50%, 75%, or 100%. The chances are high that the gene is passed on. CMT1A, a variant of CMT1, is caused by a duplication of a gene on chromosome 17 that carries the genetic instructions for producing a protein crucial in the formation of the myelin sheath.[2] This means that the gene is expressed more than it should be which causes problems that result the the myelin sheath failing to function properly.

The prefrontal cortex is known to develop in the later periods of the prenatal stages when relating to myelination, cell growth and synaptic density (Kolb et al. 2012). Since it has a prolonged development with the expression of glucocorticoid (GC) receptors, the prefrontal cortex may be prone to early insults (Kolb et al. 2012). This study was also concluded in rats that showcased a relationship between maternal stress during pregnancy and reductions of dendritic spine densities in the prefrontal cortex (Kolb et al.

In the majority of Rett Syndrome cases, it is caused by a mutation in a single gene. In 1999, it was discovered that mutation within the Methylcytosine-binding protein 2 is what eventually lead to Rett Syndrome. This gene makes a protein that is extremely necessary for the brain to function. However, the mutation is insufficient on developing this gene, or it damages the protein to the point where it may not be used. Either way, there is not enough working protein for the child to cooperate.

Genes are often named after their condition. The gene is called FMR1 gene; this acronym stands for Fragile X Mental Retardation gene. It is typical of the FMR1 gene to repeat seven to sixty times the CGG pattern. This is normally repeated approximately 30 times; however, in this instance it repeats well above the average. An individual with the syndrome may have well over 200 repeats of the gene. With such high numbers of the gene created the methyl group bind together with the C bases (or cytosine) affecting the gene and causing it to be deactivated. This gene is present in everyone and is responsible for the development of the brain and testes by producing a protein that allows other genes to work normally (Saunders, S., 1999). Due to the gene not functioning, it does not create the protein needed for brain development. This is how Fragile X Syndrome

Rett syndrome (RTT) is a rare random brain & nervous system disorder that only affects girls due to it being an X-linked mutation and although it is genetic, it is not hereditary; it rarely affects boys, when it does the symptoms are more severe and the “babies rarely live past birth” (Bhandari, 2017). The babies usually go through a normal pregnancy and start to show symptoms after the first six months; they become more prominent at “12 and 18 months, and they can be sudden or progress slowly.” (Bhandari, 2017). Symptoms include “slowed growth, trouble with breathing, no language skills, problems with hand movements, muscles, and coordination” (Bhandari, 2017). There is no cure, but the best available treatments include “standard medical care

CMT can be passed down by sex-linked chromosomes or it can be passed down through autosomal inheritance. Either way, CMT is a mutation of proteins required for the peripheral nervous system. If it’s sex-linked it means the disease is carried on the female sex chromosome X, never on the Y male chromosome. If it’s autosomal it means it’s carried in the DNA, on the genetic chromosomes. It can be recessive, needing two pairs of bad alleles, one from each parent, or it could be dominant only needing one allele from either parent. There are cases where people were affected carrying only one recessive allele, like men for instance (MDA, 2017), where males only have one X, if their X chromosome is a faulty one, it could be missing genetic information it needs to keep rebuilding proteins the body requires for reproduction of those crucial proteins. CMT can pop up and affect anyone at any given time in life, you could live with CMT your whole life and never know you have it, or you could find out you’re a carrier for CMT after you’ve passed it on to your offspring (Al-Thihli, K et al. 2012). As you can tell CMT is passed down through inheritance, we are the cause of the continuing cases for CMT, and we still don’t have a cure to treat the prior cases. It seems the disease is only continuing to be carried in more forms as we diagnose more people and disclose more cases (Vallat, Jean-Michel, 2003).

2010). The neuroinflammation is an early, non-specific immune reaction to tissue damage or pathogen invasion (Lee et al. 2010). Inflammation of the central nervous system (CNS) is characterized by increased glial activation, pro-inflammatory cytokine concentration, blood-brain-barrier permeability, and leukocyte invasion (Lee et al. 2010). Microglia are cells that support and protect neuronal functions (Lee at al. 2010). They act as the first and main form of active immune defense that orchestrate the endogenous immune response of the Central Nervous System. The microglia play a central role in the cellular response to pathological lesions such as Aβ. Aβ can attract and activate microglia, leading to clustering of microglia around Aβ deposits sites in the brain (Lee et al. 2010). Even though microglia have neuroprotective functions, neurotoxic mechanisms which involves continuous activation of microglia and toxic factors are released by microglia, which may lead to neuroinflammation (Lee et al. 2010). Astrocytes (star-shaped glial cells) are the most abundant cells in the brain and are located in the brain and spinal. Astrocytes have various functions such as: biochemical support of endothelial cells of the BBB, supplying nutrients to the nervous tissue, maintenance of extracellular ion balance, and healing the brain and spinal cord following traumatic injury (Lee et al., 2010). Chemokines are released by astrocytes which attract microglia and they further express proinflammatory products, thus increasing neuronal damage in the pathogenesis of AD (Lee et al., 2010). Astrocytes play a critical role in Aß clearance and degradation, and they also provide trophic support to neurons forming a protective barrier between Aß deposits and neurons (Wyss-Coray et al., 2003). Neurons contribute to the production of

With an abnormal number of repeats the trinucleotide sequence becomes more unstable and disease symptoms grow to be more visible. Myotonic dystrophy II (DM2) is a mutation of cellular nucleic acid binding protein (CNBP), or zinc finger protein 9. The functions of both proteins, CNBP and DMPK are uncertain, however they can be found in multiple organs and tissues in the body, including the brain, cardiac, and skeletal muscles (Ueada, Ohno & Kobayashi, 2000). Myotonic dystrophy is located on chromosome 19q13.3 and is a result of an abnormal repeat of the DNA sequence. According to Mckusick & Hartz (1986) People with DM2 can have from 75 to more than 11,000 CCTG repeats. Both DM1 and DM2 are autosomal dominant inheritable disease, which can be passed along to offspring if the parent is affected, at a 50% probability. Myotonic dystrophy is unique from most provided that “disease-causing alleles may expand in length during gametogenesis, resulting in the transmission of longer trinucleotide repeat alleles that may be associated with earlier onset and more severe disease than that observed in the parent” (Bird et al., 1999).

This gene is believed to be able to control the function of several other genes. This wasn’t discovered until 1999. The MECP2 gene is believed to contain instructions for the synthesis of a protein called methyl cytosine binding protein 2. This protein is responsible for the development of the brain and acts as one of the many biochemical switches. This can either increase gene expression or it can tell other genes to turn off and stop production of their own unique routine. Since the gene doesn’t function properly with those who have Rett Syndrome, they have an insufficient amount or structurally abnormal forms of proteins produced. This can cause other genes to be abnormally

Fragile X Syndrome was identified in the year 1991. This disability affects more males than females. Approximately 1 in 4,000 males are affected, however only 1 in 8,000 females are affected (Lombroso, 2003). Fragile X generates in the FMR1 gene. Fragile X is caused by an excessively repeating tri-nucleotide,

There are so many types of diseases and disorders in this world. Some can lead to a lifetime of pain and others can lead to mortality. Robinow syndrome is a disorder that affects few people. This rare disorder is inherited to the fetus by the parents. This disorder comes in dominant form and recessive form. In dominant form you inherit the gene from only one of the parents. In recessive form you inherit the gene from both parents. In the recessive form the syndrome comes from mutations in the ROR2 gene. In the dominant form the syndrome is caused by the mutations in the WNT5A or DVL1 gene. The genes affect the development of the patient in its first years. Robinow syndrome affects both male and females. They have

Once the MEPC2 gene was implicated in RTT there was an intense period of cohort screening in an attempt to elucidate genotypic-phenotypic associations (Weaving, 2005). As it stands there are an approximate 800 pathogenetic mutations that are currently found within the MEPC2 (Cheadle, 2000). These include missense, nonsense, frame shifts and inversions as well as large deletions which have now been identified as being present in 15% of apparently MECP2 mutation negative individuals. These large deletions would have gone undetected without the application of NGS techniques (Weaving, 2005). Work by Wolffe aimed to explore the associations between the type of MECP2 mutation and the degree of phenotypic severity. While work in this area is largely conflicted his study was concurrent with previous work concerning the view that particular mutations that were either point mutations, such as p.Arg133Cys, p.Arg294X, p.Arg306Cys and 3’ truncations resulted in a reduction in the severity of symptoms. There is also a wide consensus that missense mutations produce a less acute phenotype than nonsense mutations and that the most severe clinical features were the consequence of splice sites or large insertions or deletions (Weaving, 2005). The MEPC2 gene codes a protein, which is apart of the methyl-CpG-binding family. It contains three conserved functional domains. Work by Wolffe also examined which aspects of the protein were affected by each type of mutation. He found that Nonsense