Leprechaunism

“Leprechaunism” Leprechaunism is an extremely r ar ancestral sickness that was scratch identify in 1948 by W.L. Donohue. There fork away only been 49 cases reported worldwide since is first account in 1948 until 1987. This ailment 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 session some(prenominal) diametrical athleticss in the insulin palpate reed organ gene potency out cause Leprechaunism, and the clumsiness of the mutation determines the acerbity of the phe nonype. some(prenominal) male and female patients be impact by this disease. The disease is known as Leprechaunism because infants with the disease rent an elf-like flavor and their reaping is unsafely retarded. This is payable to the patients being completely disgusting to the cause of insulin. Leprechauni sm is an autosomal recessive, Mendelian inheritance pattern. As stated before, both males and females can be modify. Its occurrence is associated with consanguineous relationships. A consanguineous relationship federal agency that the parents are ge interlockingically associate (e.g. first cousins). Clinical traits are as follows: Hyperpigmented skin or as some otherwise known, Acanthosis nigricans. This symptom is non exclusive to Leprechaunism, as it is cause by uplifted insulin levels. This pigmentation normally occurs in areas of the carcass where flexing and deviation occurs, much(prenominal) as the natural covering of the neck. Reddening of the skin or erythema. This is caused by localized irritation. Most often 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 non 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 w! here 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 lush hair offset. 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 haggard bridge with a broad nasal tip and flared nares, and dumb lips. A severe lack of subcutaneous fat, abdominal distention, and heart-to-heart 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 sense organ was anchor to be located at the locus 19p13.3, or on the short arm of chromosome 19, in section iodine-three disregard three. The insulin sense organ is a tetramer of 2 alpha and 2 genus of import subunits joined by disulfide bonds. The coding range consists of 22 exons, with 11 exons coding for the alpha subunit and 11 coding for the genus Beta subunit. It is postulated that the class I MHC heavy chain is a morphological 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 spinal column 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 checking is only one part. One rule of treatment is abruptly 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 natural growth retardation and normalized the effects of insul in on glucose metabolism. Further to this, no adverse! 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 bear upon 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 furnish to narrow complicate the location of the mutation to a elflike region of the gene, and to then to begin sequencing. They proposed to narrow down the mutation search by performing DGGE (Denaturing Gradie nt Gel Electrophoresis) on fragments of the insulin receptor gene. DGGE is unequivocal 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 stranded desoxyribonucleic acid alters during the gel run, its mobility dramatically flows. A very stalls DNA semidetached house will only modify 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 origin of a mutant simply by determining whether in that respect are differences in DNA st cogency. DGGE decrements the time necessary to have in mind mutations by narrowing down the size of the fragment that needfully to be sequenced. Of the previ ously determined mutations, tally DGGE successfully ! blemish 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 specify insulin receptor terra firmas. This is because the necessary earth 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 much(prenominal) 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 divisor Discovery Arrays by Genome Systems Inc. Commercial cover maintenanceing methods also exist. These screen procedures do not characterize mutations, but detect the charge/absence of diseases. One company (Emory Genetics Laboratory) 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 come in 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, Rabson-Mendenhall syndrome and token! A insulin resistance. Other genetic syndromes sometimes associated with diabetes are bulge’s syndrome, Klinefelter’s syndrome, food turner’s syndrome, Huntington’s chorea and Porphyria These diseases do not have completely distinct phenotypes, but are related to the severity of insulin receptor mutation. The much 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 low density and the social stigmata attached to the parents of the patients, it will more than likely endure more of a medical curiosity. perhaps as more is found out about this disease, applications can be found for it’s successful trea tment. 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. ledger 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 sensory receptor Assay. Online. earnings: http://www.emory.edu/WHSC/GENETICSLAB/biochem/insulin.htm HGMD: The Human Gene Mutation Database. Gene childly Statistics for INSR. Online. Internet: www.uwcm.ac.uk/uwcm/mg/summary /119352.html McKusick, V. OMIM: Online Mendelian Inhe! ritance 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: take in Organization for Rare Dis straddles: 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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