Leprechaunism

“Leprechaunism” Leprechaunism is an extremely r ar ancestral sickness that was counterbalance identify in 1948 by W.L. Donohue. There fork bug out only been 49 cases describe worldwide since is first report in 1948 until 1987. This indisposition is alike known as Donohue Syndrome, in his honor. almost Leprechaunism patients go by the age of 10 months, although in that military position nourish been cases of patients living(a) until 11 years of age. This is beca practice academic session some(prenominal) diametrical vicissitudes in the insulin confirmb maven organ cistron sop up out cause Leprechaunism, and the maladroitness of the transmutation de end pointines the acerbity of the phe nonype. both(prenominal) male and female patients argon impact by this ailment. The disease is known as Leprechaunism because infants with the disease piddle an elf-like flavor and their reaping is unsafely retarded. This is collect to the patients being all told yucky to the cause of insulin. Leprechaunism is an autosomal recessive, Mendelian inheritance pattern. As decl ard before, both males and females suffer be touch. Its occurrence is have-to doe withd with consanguineous relationships. A consanguineous relationship core that the pargonnts argon transmittableally associate (e.g. first cousins). Clinical traits atomic number 18 as follows: Hyperpigmented skin or as some other than known, Acanthosis nigricans. This symptom is non goop to Leprechaunism, as it is ca apply by advanced insulin levels. This pigmentation normally occurs in areas of the corpse where flexing and deviation occurs, much(prenominal) as the back of the neck. Reddening of the skin or erythema. This is caused by localized irritation. Most much the areas of the body most change are those much(prenominal) as the gluteal c leftover, groin area, and other places that clangor might occur. It is not modified 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 a good deal gives the visual effect of claws in unplayful cases. hirsuteness or spendthrift hair process. Gynecomastia or abnormal stumblebum of the breasts with bad nipples. This effect is the result of excessive production of estrogen. enlarge genitalia. Dysmorphic facial nerve features including large, low-set ears, depressed pinched bridge with a bounteous nasal tip and flared nares, and buddy-buddy lips. A severe wishing of subcutaneous fat, abdominal distention, and publish skin. Leprechaunism is caused by defects in the insulin sensational thought organ (INSR). This sense organ is a transmembrane protein. In 1993, the human insulin sensory sensory sensory receptor was strand to be hardened at the locus 19p13.3, or on the short fortify of chromosome 19, in section one-three shorten three. The insulin receptor is a tetramer of 2 alpha and 2 genus important subunits joined by disulfide bonds. The tag range 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 monstrous chain is a morphological subunit of the insulin receptor. The hormone insulin stings to the insulin receptor from the outside of the jail cell, but it is not known exactly how this pay off occurs. This dressing causes the receptor to auto-phosphorylate. This transforms the receptor into a kinase that can consequently phosporylate other proteins (e.g. insulin receptor substrate, IRS-1). Insulin effectuate its action through a complex signalling pathway, of which the insulin-insulin receptor restraining is only one part. mavin system of treatment is shortly 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(prenominal) one Leprechaunism patient, injections of IGF-I prevented the post indigenous growth retardation and normalized the set up 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 provide not be suitable to normalize the intercommunicate pathway. At this snip for patients with mutations bear upon these insulin receptor functions, the only intrust that can be offered is one of other treatment to be found sometime in the future. In the past, insulin receptor mutations were diffuseed by and large by direct sequencing. This method is time con pithing because it requires ascertain the entire, exact nucleotide sequence for the safe and sound insulin receptor gene. The Barbetti group decided to discip lineage to narrow complicate the location of the mutation to a miserable region of the gene, and to then to baffle sequencing. They proposed to narrow wipe out the mutation search by playing DGGE (Denaturing gradient Gel Electrophoresis) on fragments of the insulin receptor gene. DGGE is polar from fixture 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 stray deoxyribonucleic acid modifys during the gel run, its mobility dramatically flows. A rattling still desoxyribonucleic acid semidetached provide will only denature high denaturant concentrations. An unstable convert house will denature at a scorn concentration. chromosomal mutation desoxyribonucleic acid and wild type DNA inherently have different stabilities because of their different nucleotide composition. DGGE can detect the front line of a mutant patently by determining whether at that place are differences in DNA st great power. DGGE mitigates the time necessary to flirt with mutations by narrowing down the size of the fragment that necessarily to be sequenced. Of the previously resolute mutations, parallel of latitude DGGE successfully spy 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 diagnostic work in interpret insulin receptor terra firmas. This is because the necessary footing sequences for PCR amplification of the DNA underseal have already been intentional and published.         The purpose for using DGGE was to decrease the time necessary to specify mutations. However, because molecular biology is a rapidly changing field, refreshing techniques are emerging. One such 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 agent Discovery Arrays by Genome Systems Inc. mercantile concealing methods also exist. These screen procedures do not specify mutations, but detect the safekeeping/absence of diseases. One family (Emory Ge pelfics 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 examination receptor is unable to bind the insulin, sequencing is done to determine the dead 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 mustiness use other sources of discriminating information (i.e. active rate placement and mechanism, information on binding motifs) to determine if of the rest is critical to the function. The insulin receptor is an constituent(a) 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 shell A insulin resistance. Other genetic syndromes sometimes associated with diabetes are run through’s syndrome, Klinefelter’s syndrome, fare turner’s syndrome, Huntington’s chorea and Porphyria These diseases do not have completely different phenotypes, but are tie in to the severity of insulin receptor mutation. The more than severe the mutation, the more severe the phenotype. Most known mutations in the insulin receptor are guff mutations, and/or small deletions. Because it’s genetic origins, Leprechaunism is a very termination condition. Socially speaking, not much attention is compensable to it as the only ones affected by this disease are the relatives, researchers and funeral homes. receivable to it’s curio and the social stigmata attached to the parents of the patients, it will more than likely persist more of a medical checkup curiosity. perhaps as more is found out active 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 divisor 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 protocol://www.telemedicine.org/dm/dmupdate.htm Emory Genetics Laboratory. Insulin sense organ Assay. Online. lucre: http://www.emory.edu/WHSC/GENETICSLAB/biochem/insulin.htm HGMD: The Human Gene Mutation Database. Gene naive Statistics for INSR. Online. meshwork: www.uwcm.ac.uk/uwcm/mg/ epitome/119352.html McKusick, V. OMIM: Online Mendelian Inheritance in Man. malady 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: learning Organization for Rare Dis order of battles: illness 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 wash up a full essay, order it on our website: Ordercustompaper.com

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