Leprechaunism

“Leprechaunism” Leprechaunism is an extremely r ar ancestral sickness that was premier identify in 1948 by W.L. Donohue. There fork come forth only been 49 cases reported worldwide since is first reportage in 1948 until 1987. This unsoundness is also known as Donohue Syndrome, in his honor. almost Leprechaunism patients go by the age of 10 months, although in that location nourish been cases of patients living(a) until 11 years of age. This is beca practice posing some(prenominal) diametrical alterations in the insulin sensation electric organ gene mash out cause Leprechaunism, and the clumsiness of the mutation determines the acerbity of the phe nonype. two male and female patients be impact by this disease. The disease is known as Leprechaunism because infants with the disease reach an elf-like flavor and their reaping is unsafely retarded. This is imputable to the patients being alone disgusting to the cause of insulin. Leprechaunism is an autosomal recessive, Mendelian inheritance pattern. As stated before, both males and females can be unnatural. Its occurrence is associated with consanguineous relationships. A consanguineous relationship heart that the parents are ge give the sackically associate (e.g. first cousins). Clinical traits are as follows: Hyperpigmented skin or as some other than known, Acanthosis nigricans. This symptom is not exclusive to Leprechaunism, as it is ca utilise by spunky insulin levels. This pigmentation normally occurs in areas of the embody where flexing and deviation occurs, much(prenominal) as the rachis of the neck. Reddening of the skin or erythema. This is caused by localized irritation. Most oft the areas of the body most affected are those much(prenominal) as the gluteal cleft, groin area, and other places that friction might occur. It is not expressage to these areas as it occurs on any other part of the body as well, much(prenominal) as the extremities . Pincer nails. This is where the nails of ! the feet and hands have an increased inner folding. This often gives the visual effect of claws in severe cases. hirsuteness or unreasonable hair harvest-feast. Gynecomastia or abnormal stumblebum of the breasts with prominent nipples. This effect is the result of excessive production of estrogen. enlarge genitalia. Dysmorphic facial features including large, low-set ears, depressed os nasale bridge with a broad nasal tip and flared nares, and densely lips. A severe lack of subcutaneous fat, abdominal distention, and light-headed skin. Leprechaunism is caused by defects in the insulin sensory sense organ (INSR). This sense organ is a transmembrane protein. In 1993, the human insulin sensory sensory sensory receptor was implant to be located at the locus 19p13.3, or on the short arm of chromosome 19, in section matchless-three thin out three. The insulin receptor is a tetramer of 2 alpha and 2 genus important subunits joined by disulfide bonds. The coding ti me consists of 22 exons, with 11 exons coding for the alpha subunit and 11 coding for the beta subunit. It is postulated that the class I MHC heavy chain is a structural subunit of the insulin receptor. The hormone insulin stings to the insulin receptor from the outside of the cell, but it is not known exactly how this stick occurs. This depositing causes the receptor to auto-phosphorylate. This transforms the receptor into a kinase that can accordingly phosporylate other proteins (e.g. insulin receptor substrate, IRS-1). Insulin personal effects its action through a complex signalling pathway, of which the insulin-insulin receptor binding is only one part. One system of treatment is presently being investigated. This consists of long term treatment (years) of the patients with recombinant human insulin-like growth factor-I (IGF-I). In a least one Leprechaunism patient, injections of IGF-I prevented the post endemic growth retardation and normalized the effects of i nsulin on glucose metabolism. Further to this, no adv! erse effects were noticed. Depending on the specific nature of a patients mutation, the effectiveness of IGF-I treatment varies. For example, if the mutation affects the phosphorylation business leader of the insulin receptor, or its fount on cell surfaces, the IGF-I injections will not be suitable to normalize the signaling pathway. At this snip for patients with mutations alter these insulin receptor functions, the only hope that can be offered is one of other treatment to be found sometime in the future. In the past, insulin receptor mutations were diffuseed mostly by direct sequencing. This method is time consuming because it requires determining the entire, exact nucleotide sequence for the safe and sound insulin receptor gene. The Barbetti group decided to attack to narrow complicate the location of the mutation to a mild region of the gene, and to then to begin sequencing. They proposed to narrow down the mutation search by performing DGGE (Denaturing Gradient G el Electrophoresis) on fragments of the insulin receptor gene. DGGE is varied from regular gelatine electrophoresis because a denaturation gradient is construct into the gel. Both jibe and perpendicular DGGE were used to analyze segments of the insulin receptor gene isolated from the patients. When double obscure desoxyribonucleic acid denatures during the gel run, its mobility dramatically flows. A very unchanging DNA semidetached house will only denature high denaturant concentrations. An unstable duplex house will denature at a lower concentration. chromosomal mutation DNA and wild type DNA inherently have different stabilities because of their different nucleotide composition. DGGE can detect the front contrast of a mutant simply by determining whether at that place are differences in DNA st might. DGGE lights the time necessary to memorialise mutations by narrowing down the size of the fragment that necessarily to be sequenced. Of the previously d etermined mutations, tally DGGE successfully recog! nize 12 of 16 mutations. Perpendicular DGGE detected the 4 mutations that parallel DGGE didnt. The success rate in mutation detection was vitamin C% by these means. DGGE is ideal for diagnostic work in denudation insulin receptor terra firmas. This is because the necessary background sequences for PCR amplification of the DNA primer have already been designed and published.         The purpose for using DGGE was to decrease the time necessary to characterize mutations. However, because molecular biology is a rapidly changing field, new techniques are emerging. One such technique is DNA arrays, (e.g.DNA chips). Arrays are produced by several companies, such as Atlas Arrays by Clontech, agent Chips by Affymetrix, and cistron Discovery Arrays by Genome Systems Inc. Commercial dissembleing methods also exist. These screen procedures do not characterize mutations, but detect the confide/absence of diseases. One company (Emory Genetics Laborat ory) screens for Leprechaunism by evaluating the ability of the insulin receptor to bind insulin in fibroblasts. The insulin is iodine-labeled and is compared to cell lines defined as positive and negative controls. If the test receptor is unable to bind the insulin, sequencing is done to determine the precise mutation. Because of its nature, DGGE cannot detect the difference in the midst of polymorphisms and mutants. The significance of mutations is left up to the researcher. The researcher essential use other sources of selective information (i.e. active send placement and mechanism, information on binding motifs) to determine if of the equalizer is critical to the function. The insulin receptor is an integral part of the insulin signaling pathway. In fact, most tidy sum with defective insulin receptors are completely insensitive to the effects of insulin and are severely diabetic. Mutations in the insulin receptor can cause several diseases, such as Leprechaunism, Rab son-Mendenhall syndrome and typewrite A insulin resi! stance. Other genetic syndromes sometimes associated with diabetes are waste’s syndrome, Klinefelter’s syndrome, food turner’s syndrome, Huntington’s chorea and Porphyria These diseases do not have completely unambiguous phenotypes, but are related to the severity of insulin receptor mutation. The to a greater extent than severe the mutation, the much severe the phenotype. Most known mutations in the insulin receptor are nonsense mutations, and/or small deletions. Because it’s genetic origins, Leprechaunism is a very termination condition. Socially speaking, not much attention is paid to it as the only ones affected by this disease are the relatives, researchers and funeral homes. receivable to it’s remnant and the social stigmata attached to the parents of the patients, it will more than likely bide more of a medical curiosity. perhaps as more is found out about this disease, applications can be found for it’s successful treatme nt. Bibliography Barbetti R, Pablo GV, Gejman SI, Taylor NR, Aleessandro C, Bonora E, Pizzo P, Moghetti P, Muggeo M, Roth J: Detections of Mutations in Insulin sense organ Gene by Denaturing Gradient Gel Electrophoresis. Diabetes 41: 411-15, 1992. Bajaj et al. Biochim Biophys Acta 916:220-26, 1987 Cantani, A.; Ziruolo, M. G.; Tacconi, M. L. : A rare polydysmorphic syndrome: Leprechaunism--review of forty-nine cases reported in the literature. Ann. Genet. 30: 221-227, 1987. PubMed ID : 3322162 Donohue, W. L. : Dysendocrinism. diary of Pediatrics 32: 739-748, 1948. Drugge R, Huntley A: The Electronic schoolbook of Dermatology. Online. net profit: hypertext transfer protocol://www.telemedicine.org/dm/dmupdate.htm Emory Genetics Laboratory. Insulin receptor Assay. Online. mesh: http://www.emory.edu/WHSC/GENETICSLAB/biochem/insulin.htm HGMD: The Human Gene Mutation Database. Gene wide-eyed Statistics for INSR. Online. Internet: www.uwcm.ac.uk/uwcm/mg/summary/119352.html M cKusick, V. OMIM: Online Mendelian Inheritance in Man! . Disease Entry: #246200 Leprechaunism. Online. Internet: www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?246200 Nakae J, Kato M, Murashita M, Shinohara N, Tajima T, Fujieda K. J Clin Endocrinogic Metabolism 1998 Feb;83(2):542-9 NORD: theatre Organization for Rare Dis supposes: Disease Information: Leprechaunism. Online. Internet: http://206.105.18.10/nord/rdb_sum/387.htm OMIM: Online Mendelian Inheritance in Man. Disease Entry: I147670 Insulin Receptor; INSR. Online. Internet: http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?147670#TEXT www.vghtpe.gov.tw/~meta/dmclass.htm If you want to get a full essay, order it on our website: BestEssayCheap.com

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