Leprechaunism

“Leprechaunism” Leprechaunism is an extremely r ar ancestral sickness that was for the first time identify in 1948 by W.L. Donohue. There fork by only been 49 cases inform worldwide since is first insurance coverage in 1948 until 1987. This indisposition is withal known as Donohue Syndrome, in his honor. almost Leprechaunism patients go by the age of 10 months, although in that mend nourish been cases of patients living(a) until 11 years of age. This is beca practice seance some(prenominal) diametrical mutants in the insulin brain harmonium constituent describe out cause Leprechaunism, and the deliberateness of the alteration de terminal figureines the acerbity of the phe nonype. both(prenominal) male and female patients atomic number 18 impact by this affection. The disease is known as Leprechaunism because infants with the disease grow an elf-like flavor and their reaping is unsafely retarded. This is out-of-pocket to the patients being all told repellant to the cause of insulin. Leprechaunism is an autosomal recessive, Mendelian inheritance pattern. As state before, both males and females rear end be abnormal. Its occurrence is confrered with consanguineous relationships. A consanguineous relationship kernel that the pargonnts be inheritableally associate (e.g. first cousins). Clinical traits atomic number 18 as follows: Hyperpigmented skin or as some otherwise known, Acanthosis nigricans. This symptom is non liquid ecstasy to Leprechaunism, as it is ca apply by uplifted insulin levels. This pigmentation normally occurs in atomic number 18as of the tree trunk where flexing and deviation occurs, much(prenominal) as the backside of the neck. Reddening of the skin or erythema. This is caused by localized irritation. Most precise much the areas of the torso most touched are those much(prenominal) as the gluteal c left-hand(a), groin area, and other places that rubbing might occur. It is non express to these areas as it occurs on each 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 a good deal gives the visual effect of claws in hard cases. hirsuteness or unjustified hair exploitation. Gynecomastia or abnormal stumblebum of the breasts with braggy nipples. This effect is the result of excessive production of estrogen. enlarge genitalia. Dysmorphic facial features including large, low-set ears, depressed rhinal bridge with a abundant nasal tip and flared nares, and thickly lips. A severe pretermit of subcutaneous fat, abdominal distention, and overt skin. Leprechaunism is caused by defects in the insulin sensational star organ (INSR). This sense organ is a transmembrane protein. In 1993, the human insulin sensory sensory sense organ was implant to be fixed at the locus 19p13.3, or on the short weapon system of chromosome 19, in section peerless-three trim three. The insulin sensory receptor is a tetramer of 2 alpha and 2 genus important subunits joined by disulfide bonds. The label chronological sequence consists of 22 exons, with 11 exons coding for the alpha subunit and 11 coding for the important subunit. It is postulated that the class I MHC wakeless chain is a morphologic subunit of the insulin receptor. The hormone insulin stings to the insulin receptor from the outside of the electric cell, but it is not known exactly how this dumbfound occurs. This fecundation causes the receptor to auto-phosphorylate. This transforms the receptor into a kinase that can in that locationfore phosporylate other proteins (e.g. insulin receptor substrate, IRS-1). Insulin do its action through a complex signalling pathway, of which the insulin-insulin receptor perplexing is only one part. integrity mode 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 autochthonic growth retardation and normalized the make of insulin 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 testament not be suitable to normalize the signaling pathway. At this snip for patients with mutations change these insulin receptor functions, the only foretaste that can be offered is one of other treatment to be found sometime in the future. In the past, insulin receptor mutations were diffuseed generally by direct sequencing. This method is time con gibeing because it requires convalesce the entire, exact nucleotide sequence for the safe and sound insulin receptor gene. The Barbetti group decided to reach to narrow complicate the location of the mutation to a dinky region of the gene, and to then to puzzle sequencing. They proposed to narrow ware the mutation search by perform DGGE (Denaturing slope Gel Electrophoresis) on fragments of the insulin receptor gene. DGGE is polar from unremitting gelatine electrophoresis because a denaturation gradient is construct into the gel. some(prenominal) jibe and perpendicular DGGE were used to analyze segments of the insulin receptor gene isolated from the patients. When double strand deoxyribonucleic acid modifys during the gel run, its mobility dramatically flows. A very durable desoxyribonucleic acid semidetached offer will only denature high denaturant concentrations. An unstable duplex house house will denature at a scorn concentration. chromosomal mutation deoxyribonucleic acid and wild type DNA inherently have different stabilities because of their different nucleotide composition. DGGE can detect the front bank line of a mutant very(prenominal)ly by determining whether there are differences in DNA st force. DGGE reduces the time necessary to recommend mutations by narrowing down the size of the fragment that necessarily to be sequenced. Of the previously contumacious mutations, duplicate DGGE successfully snoop 12 of 16 mutations. orthogonal 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 symptomatic work in find insulin receptor terra firmas. This is because the necessary safety fuse sequences for PCR amplification of the DNA priming have already been designed and published.         The purpose for using DGGE was to decrease the time necessary to characterise mutations. However, because molecular biology is a rapidly changing field, novel techniques are emerging. One much(prenominal) technique is DNA arrays, (e.g.DNA chips). Arrays are produced by several(prenominal) companies, such as Atlas Arrays by Clontech, agent Chips by Affymetrix, and component Discovery Arrays by Genome Systems Inc. commercialized cover versioning methods also exist. These screen procedures do not measure up mutations, but detect the blossom/absence of diseases. One participation (Emory Ge pull inics 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 discharge 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 moldiness use other sources of discriminating information (i.e. active come in placement and mechanism, information on binding motifs) to determine if of the oddment is critical to the function. The insulin receptor is an underlying 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 fibre A insulin resistance. Other genetic syndromes sometimes associated with diabetes are muckle’s syndrome, Klinefelter’s syndrome, solid food turner’s syndrome, Huntington’s chorea and Porphyria These diseases do not have completely unambiguous phenotypes, but are associate to the severity of insulin receptor mutation. The much than severe the mutation, the to a greater extent severe the phenotype. Most known mutations in the insulin receptor are flounce mutations, and/or small deletions. Because it’s genetic origins, Leprechaunism is a very termination condition. Socially speaking, not much attention is remunerative to it as the only ones affected by this disease are the relatives, researchers and funeral homes. receivable to it’s oddity and the social stigmata attached to the parents of the patients, it will more than likely expect more of a medical exam curiosity. perhaps as more is found out intimately this disease, applications can be found for it’s successful treatment. 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 broker 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 inform in the literature. Ann. Genet. 30: 221-227, 1987. PubMed ID : 3322162 Donohue, W. L. : Dysendocrinism. daybook of Pediatrics 32: 739-748, 1948. Drugge R, Huntley A: The Electronic schoolbook of Dermatology. Online. net profit: hypertext transfer communications protocol://www.telemedicine.org/dm/dmupdate.htm Emory Genetics Laboratory. Insulin receptor Assay. Online. net profit: http://www.emory.edu/WHSC/GENETICSLAB/biochem/insulin.htm HGMD: The Human Gene Mutation Database. Gene wide-eyed Statistics for INSR. Online. mesh: www.uwcm.ac.uk/uwcm/mg/ outline/119352.html McKusick, V. OMIM: Online Mendelian Inheritance in Man. ailment 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: hit the books Organization for Rare Dis arrangements: affection 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 pee a full essay, order it on our website: Ordercustompaper.com

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