According to Ralf Sudbrak and other authors, a mutation in the gene ATP2C1 is associated with the cause of the Hailey-Hailey Disease. The disease is an autosomal dominant inherited skin disorder. The defect in the gene alters the expression of calcium pumps thus altering calcium signaling and their role in maintaining the epidermis (Sudbrak et al. 1). The gene encodes a protein that acts as a calcium pump in cells. This protein pumps calcium ions into the lumen of the Golgi apparatus. Calcium ions are vital in cell-to-cell adhesion processes and differentiation, and if the calcium pump does not function properly, the affected cells will not stick together, thus causing damage to the skin (Szigeti 1). The protein encoded by ATP2C1 has the same transmembrane organization, including all the conserved domain characteristics like ATP binding, phosphorylation, and conformational changes enzymes, of Phosphorylation-type (P-Type) ATPases (Sudbrak et …show more content…
The P-type ATPases help maintain the concentration of free calcium in the cytosol at low levels (Lodish et al 1). Dysfunction of the ATP2C1 protein encoded pump leads to a build-up of calcium in the cytosol and decreases concentration in the lumen of the Golgi, which leads to impaired signaling pathways that regulate cell adhesion and differentiation of cell epidermis. The most noticeable feature of Hailey-Hailey Disease is a defect in keratinocyte adhesion in layers of the epidermis (Sudbrak et al. 6). The ion transport pump encoded by a mutated ATP2C1 does not properly uptake the free calcium in cytosol due to either the pump functioning incorrectly or not being there at all. The cytosol is now over concentrated with calcium, while the lumen has very little available calcium. The lack of calcium in the lumen inhibits differentiation of cell epidermis since there is no calcium to regulate keratinocytes and
Lysosomes contain hydrolytic enzymes which function in the acid of the lysosome and are meant to be secreted not as wastes into the extracellular fluids, but as secretory proteins into an intracellular organelle. When one of these enzymes is dysfunctional, the catabolism of its macromolecule does not completely occur and there is a buildup of the macromolecule inside the lysosome. This results in great numbers of large lysosomes which begin to interfere with the normal functions of the cell. This disorder is called lysosomal storage disorder. These disorders can eventually lead to the dysfunction of the organs. The organs affected by the disorder are determined by two factors: 1) The location in the body where the macromolecules that are to be catabolized are found, and 2) The location where the catabolism occurs.
Brunner syndrome is a recessive X-linked disorder characterized by impulsive aggressiveness and mild mental retardation associated with MAOA deficiency. According to Brunner, it is a rare genetic disorder with a mutation in the MAOA gene (monoamine oxidase A gene). It is characterized by lower than average IQ (typically about 85), is a problematic impulsive behavior (such as arson, hypersexuality and violence), is also a sleep disorders and mood swings. Brunner syndrome was first discover by Hens G. Brunner; his findings has been used to argue genetics, and the behavior can cause criminal activity. Evidence supporting the genetic defense stems from both Brunner’s findings and a series of studies on mice have proven correlation
FOP occurs randomly and is not inherited. Experts believe that one cause of fibrodysplasia ossificans progressiva is born with mutations in the ACVR gene what provides the body with instructio...
The widespread involvement of Retinal Pigment Epithelium (RPE), flat (placoid) nature of the lesions and absence of overlying serous retinal detachment and minimal choroidal involvement lead Gass to conclude RPE was primary focus of inflammation.(1) ...
ACHONDROPLASIA is known as being undersized, or less than 50in. in height. Having short limbs, a normal sized trunk, large head with a depressed nasal bridge and small face. This is a result of a disease in the thyroid gland. It can also be caused by Down syndrome or absorption, a cartilaginous tissue during the fetal stage. Hypochondroplasia, a mild form of dwarfism. Spinal tuberculosis and the deficiency of the pituitary gland secretions. Treatment with thyroxin or thyroid extract early in childhood results in normal growth and development. Somatrophin, also known as the human growth hormone is secreted by the anterior pituitary. Respiratory problems start to occur in infants. Symptoms of problems include snoring and sleeping with neck in a hyperextended condition. The limbs have rhizometic shortening. The legs are straight in infantry but when a child. He begins walking they develop a knock-knee position. When the child continues to walk legs begin to have a bowed-leg look. Occasionally, these curvatures are fixed. As the child continues to walk the kyphosis disappears and the back assumes a lordotic posture. If a delay in child’s walking occurs, the spine should be monitored closely for signs of gibbous formation. In infancy, hypercephalus can occur. Infants head circumference should be monitored close . Monthly checks of head circumference must be monitored. Radiologic studies are indicated if head circumference raises to disproportionately, or if symptoms of hydrocephalus. Child’s pediatrician should have a copy of head circumference curves for children with achondroplasia. Radiologic procedures for dwarfism include head ultrasound, C-T scan, or MRI of the head. If intervention is necessary, a ventriculoperitoneal shunt is placed relieving the pressure. Infants should also be monitored for foramen magnum compression. It is the opening at the base of the skull in which the brain stem and cervical spinal cord exit. When you have achondroplasia the foramen magnum is compressing the brain stem and spinal cord. Symptoms of narrowing include apnea the cessation of breathing and cervical myleopathy. C-T scans and MRI scans are done to examine the size of the infectious foramen magnum. A neurosurgical procedure called a foramen magnum decompression is executed to alarge foramen and alleviate further symptoms. Adolescents are at risk of getting lumbosacral spinal stenosis. The lumber spinal cord or nerve roots become compressed producing nerosurgical symptoms. Initial symptoms including weakness, tingling, and pain of the legs. Pain usually alleviated by assuming a squatting position.
Mutations within the liver/bone/kidney alkaline phosphatase gene (ALPL) that encodes for tissue non-specific alkaline phosphatase (TNAP) inhibits the mineralization of bone by causing a deficiency of TNAP (Mornet 2008). Regularly, TNAP is dephosphorylated and the inorganic phosphate that is knocked off is used for hydroxyapatite crystallization. If inorganic pyrophosphates (PPi), which are formed when ATP is hydrolyzed into AMP, are not dephosphorylated by TNAP, then hydroxyapatite deposition is inhibited (Mornet 2008).
Twin studies have been used to distinguish between genetic and environmental factors for many disorders in the general population including ectodermal dysplasia, Ellis-van Creveld, and anencephaly. This review focuses on genetic disorders affecting monozygotic, dizygotic, and conjoined twins to gain a better understanding of them. Many studies focus on twins because they have a nearly identical genome, which eliminates environmental factors. In case studies, the concordance rates in monozygotic twins have supported that certain disorders were caused by genetics and not the environment. The discordant values in twins will also be evaluated briefly. Twinning studies have also shown linkages between specific disorders and the genes responsible for them. Knowing the location of these genes allows patients to be treated quickly and efficiently. This paper will discuss the possible causes of twinning and the various methods of identifying abnormalities in twins. These methods also allow preventive measures against the rise of birth defects during prenatal development. Epigenetics in twins is also viewed through the perspective of effects on them. Treatments for genetic disorders in twins are reviewed, ranging from the restoration of malformed teeth to the separation of conjoined twins. Support groups for twins in treatment, and their families are also briefly reviewed.
ACH, is an interesting disease, one that after many years of research still remains a partial mystery. The fact that a single nucleotide on one chromosome can so greatly affect an individual is astounding, especially coupled with the fact that this mutation is so homogenious in genotype and phenotype. With more skeletal dysplasias being connected to FGFR3, research has increased to fully determine and define the pathways involved with this gene. Determining the reason for such a high mutation frequency and the link to paternal age are also being looked into. Once there is more understanding of how this mutation affects the body, treatments and possibly cures can be found for these individuals.
Turner’s Syndrome, which is one of the most common chromosomal abnormalities, is defined as “a syndrome with a chromosome count of 45 and only one X chromosome.” Turner’s was first described in 1938. Henry Turner, an endocrinologist from Oklahoma City, was the first to discover this syndrome. He was curious about why seven of his female patients, six adolescents and one adult, who he was treating for dwarfism and lack of development, were not responding to the treatments. He described the women as not matured, with short necks and low hairlines in the back, and an increased angle at which the elbow was bent. After many tests, the results showed that all of the women were missing an X chromosome.
Harlequin Ichthyosis is a rare genetic mutation that affects the thickness of the skin. In order for a child to inherit this mutation, both of their parents must be carriers of the autosomal recessive gene. This gene will affect chromosome 2q35 by the deletion mutation. This mutation causes a changes in the ABCA12 gene. This gene produces the ABCA12 protein, which carries lipids to the epidermis of the skin. Without the ABC12 protein, the epidermis will not get the lipids needed to hold the skin together, which in result will cause water lose in the body. Not only is the ABCA12 protein used in the transportation of lipids, it is also a key component in the tissue of many major organs. For example the lungs, liver, and the stomach.
problems within the specific ion channels known to cause the disease. The goal of the
A genetic disorder weakening the vertical linkage between the peripheral protein membrane and the integral protein membrane can cause reduction of membrane surface, reduction ratio of surface area to volume, and formation of spherocytes, sphere shaped RBCs. An example of this would be a weaken linkage between the band-3-protein and ankryin-1 (Perrotta, Gallagher, & Mohandas, 2008). This is a result of heterogeneous alterations in genes encode for proteins responsible for binding cite of the RBC’s inner membrane skeleton to its outer lipid bilayer. An inherited abnormality in RBC’s cause by membrane protein defects is known as Hereditary Spherocytosis (HS). The most common cause of HS is the mutations in the gene encoding the membrane protein ankyrin-1 (Gallagher, Steiner, Liem, Owen, Cline, Seidel, Garrett, & Bodine, 2010).
Tamparo, C. D. & Lewis, M. A. (2011). Diseases of the human body. Philadelphia, PA: F.A. Davis Company.
NIH, National Center for Biotechnology Information. (2015). Cyclothymic Disorder, ncbi.nlm.nih.gov Web. 22 July 2015. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002517
Most individuals are either related to or know someone who is effected by some type of disability. Many of these disabilities are caused by genetic disorders. Genetic disorders may alter physical appearance and cause mild to severe mental retardation. Fragile X syndrome, Down syndrome, Turners syndrome and many other syndromes result from a mutation of a chromosome, an extra chromosome, or too few chromosomes.