Identification of novel mutations of the ATP7A gene and prenatal diagnosis of Menkes disease by mutation analysis (DNA 분석을 이용한 ATP7A 유전자의 새로운 돌연변이 발견과 멘케스병의 산전 진단)
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- Journal of Genetic Medicine
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- v.4 no.1
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- pp.38-44
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- 2007
Purpose : Menkes disease is an X-linked recessively inherited disorder caused by the mutation of the ATP7A gene encoding copper-transporting P-type AT Pase. The phenotypic features are progressive neurological degeneration, mental retardation, loose skin, and vascular complications. Early diagnosis and treatment are very important for the prognosis of Menkes disease. Here, we describe nov el mutations of the ATP7A gene and prenatal diagnosis by mutation analysis. Methods : Five unrelated Korean Menkes patients were included in this study. They presented with depigmented wool-like hair, progressive neurologic deterioration, and hypotonia in infancy. Serum copper and ceruloplasmin levels w ere decreased. Brain magnetic resonance imaging revealed tortuous intracranial vessels. Mutation analysis has been carried out using cDNA from cultured skin fibroblasts or genomic DNA from peripheral leukocytes. Prenatal diagnosis was performed in two cases using chorionic villi samples or amniocytes. Results : Four novel mutations have been identified from four different families; c.3511+1G>A (p.E1099_N1171delinsMfsX 18), c.4005+5 G>A (p.V1268_R1335del), c.1870_2172del (p.S624_Q724del), and c.3352 G>A (p.G1118S). T he remaining one was previously reported (c.1933 C>T (p.V 1268_R1335del)). On prenatal DNA analysis, one w as diagnosed as normal, while the other turned out to be a female heterozygote with p.S624_Q724del mutation of the ATP7A gene. Conclusion : We identified 4 novel mutations of the ATP7A gene. Prenatal diagnosis in families at risk is critical in order to choose preventiv e options including an early treatment with copper-histidine therapy or therapeutic termination. Most mutations of the ATP7A gene were frame-shift mutations and prenatal diagnosis has been successfully carried out.
Purpose : The purpose of this study was to evaluate the clinical utility of rapid detection of Down syndrome and Edward syndrome by Interphase Fluorescence in Situ Hybridization (FISH) analysis. Methods : Aretrospective study in 309 cases of amniotic fluid samples, analysed by interphase FISH with DNA probes specific to chromosome 18 and 21, was performed. All FISH results w ere compared with conventional cytogenetic karyotypings. Results : The results were considered as informative and they were obtained within 48 hrs. A case of Down syndrome and a case of Edward syndrome were diagnosed by FISH and confirmed by subsequent cytogenetic analysis. In 12 cases with normal FISH results, the cytogenetic analysis showed a case of partial trisomy 22, three cases of sex chromosomal aneuploidy, two cases of mosaicism, two cases of microdeletion, and four cases of structural rearrangement. Conclusion : FISH is a rapid and effective diagnostic method, which can be used as an adjunctive test to cytogenetic analysis, for prenatal identification of chromosome aneuploidies. For the more genome-wide screening with variety of probes, the technique of FISH is both expensive and labor-intensive.
Purpose : Glycogen storage disease type III (GSD-III) is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme, amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), is responsible for the debranching of the glycogen molecule during catabolism. The disease shows clinical and biochemical heterogeneity, reflecting genotype-phenotype heterogeneity among different patients. In this study, we aim at analyzing mutations of the AGL gene in three unrelated Korean GSD-III patients, and characterizing their clinical and laboratory findings. Methods : We characterized the clinical features of three unrelated Korean GSD-III patients by biochemical, histological and imaging studies. The 35 exons and part of exon-intron boundaries of AGL were analyzed by direct sequencing using genomic DNA extracted from the peripheral leukocytes of patients. Results : Diverse clinical features were observed in these patients including hepatomegaly (all patients), seizures (patient 2), grow th failure (patients 1 and 2), hyperlipidemia (patients 1 and 3), raised transaminase and creatine kinase concentrations (all patients), and mild cardiomyopathy (patient 2). Liver transplantation w as performed in patient 2 due to progressive hepatic fibrosis. A dministration of uncooked corn starch maintained normoglycemia and improved biochemical and growth profiles. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 had c.1510_1511insT (p.Y 504L fsX 10), and patient 3 had c.3416 T >C (p.L 1139P) and c.1735+1 G>T (p.Y 538_R578delfsX 4) mutations. A part from the p.R428K mutation, the 4 other substitutions identified w ere nov el. Conclusion : GSD-III patients display variable phenotypic characteristics resembling those of GSD-Ia. Molecular defects in the AGL gene of Korean GSD-III patients are genetically heterogeneous.
The seasonal variation in lipids, and fatty acid composition of neutral lipid(NL) and phospholipid(PL) contained in the muscles of hibernant fish(loach) were investigated. In the investigation, four groups of wild loaches ere used, those caught May, 1993(before spawning period), August, 1993(after spawning period), November, 1993(just before hibernation) and March, 1994(just after hibernation). The NL was the most abundant in muscle lipid, followed by PL and glycolipid(GL), and also the composition and variation patterns were almost similar between female and male throughout all the periods. NL content began to increase gradually after March and came to the maximum in August(under 90%) ; hereafter got to decrease gradually again and came to the minimum in March of the next year(under 60%). While the variation-pattern of GL and PL was in inverse proportion with that of NL and their content came to the maximum in March of the next year. The NL and PL fractions were mainly consisted of triglyceride and phosphatidyl choline respectively, and both of the contents showed the highest value in August, the lowest in March of the next year. The major fatty acids in NL fraction were 16:0, 16:1, 18:1, 18:2 and 18:3(
Khori(高麗) refers to the Chaabog(reindeer) that live on lichens(蘚) on Mt. Soyon(鮮) in which pastures are the cold and dry plateau of North Eurasia. Thus, the origin region of the Khori or Koguryo that are the ancestors of the reindeer-herding pastoral nomads(馴鹿 遊牧民) can be said to be the Steppe-Taiga-Tundra pastoral areas of North Eurasia and North America. When the pastoral nomads moved on to the great mountain(大山) zone of the Jangbaek(長白) to the Baekdu(白頭) Mountains, they could have been in contact with pastoral farmers or agricultural farmers living there and they became the farmers remaining on agricultural farms. They were the Koryo people, the ancestors of Korea. Staying in one place, they gradually forgot the origin of their reindeer-herding pastoral nomadic history in the Northwest area of Mt. Soyon, the small mountain(小山) zone of the Steppe-Taiga-Tundra pastoral areas. In other words, they lost their identity as reindeer-herding pastoral nomads when they entered the agricultural area after leaving the pastoral area. However, since their basic genes had already formed when they lived on the cold and dry plateau of North Eurasia, it is possible to study their pastoral nomadic history focusing on 'the minority living in the broad area(廣域少數)', by utilizing highly advanced biotechnological science and focusing on genes and information technology innovation, and removing various past hindrances in research. Therefore, it is not so difficult to restore the reindeerherding pastoral nomadic history of the Koguryo(高句麗) people and secure their pastoral nomadic identity, of which the first steps have already been taken into their historical stages. The Eurasian continent and the Korean peninsula, especially the cold and dry plateau of North Eurasia and the Korean peninsula have been closely related to each other ecologically and historically. They can never be a separate space at all. The Eurasian continent lies horizontally east to west and thus, the continent forms an isothermal zone. Also, since the time of producing their own foods, it was relatively easy for people with their technology to move to other places owing to the pastoral nomadic characteristic of mobility. Unlike the Chungyen(中原) region, western Asia and the regions covering the Siberia-Manchu-Korean peninsula where food production revolution was first made were connected to the Mongolian lichens route(蘚苔之路: Ni, ukinii jam) and steppe roads. Although the ecological conditions of nature have changed a bit throughout a long history, it was natural for the many tribes in North Asia living on the largest Steppe-Taiga-Tundra area in the world to have believed 'the legends related to animals in relation to their founders and ancestors(獸祖傳說)'. Assuming that Siberian tigers and the tigers living on Mt. Baekdu were connected ecologically and genetically because of the ecological characteristics of the animals, and their migration from plateau to plateau, we would suspect that the Chosun(朝鮮) tribe living on Mt. Baekdu were ethnically and culturally more closely connected to the farther removed Ural-Altai tribes that lived on the cold and dry plateau region than to the Han(i14;) tribe who lived in Chungyen(中原) that was close to Mt. Baekdu. More evidence is the structure of the Korean language which has the form of 'Subject + Object + Verb', which is assumed to have originated from the speedy lifestyle of the reindeer-herding pastoral nomads. The structure is quite different from that of the Han(漢) language, which is based on agricultural life. Also, it is natural for reindeer riding reindeerherding pastoral nomads or horse-riding sheep-herding pastoral nomads(騎馬, 羊遊牧民) to have held military and political power over the region and eventually to have established an ancient pastoral nomadic empire in the process of their conquest of agricultural regions. The stages for founding global empires in the history of mankind maybe largely divided into two, in terms of ecological conditions and occupations. They are the steppes and the oceans. Of course, the steppe-based empires were established based on the skills to deal with horses and the ability to shoot arrows while riding horses, along with the use of iron ware in the 8th century BC. The steppe-based empires became the foundation for an oceanic empire, which could have been established by the use of warships and warship guns since the 15th Century. Based on those facts, we know that Chosun, Puyo(夫餘), and Koguryo are the products of a developmental process of pastoral nomadic empires on the steppes. Maybe we can easily find the pastoral nomadic identity of the Koguryo more than we expected when we trace the origins and history of the Korean tribe living in the pastures located in the northwest area of Mt. Jangbaek by focusing on pastoral nomadic mobility and organization just as we have investigated the historic origins of Anglo-Saxons in America by focusing on the times before the 15th Century. In the process, we should keep in mind that English culture originated from the Industrial Revolution and was directly delivered to the American continent, although America was far from England and was not an intermediate point on long sojourns either. Further, American culture came back to England in a more advanced form later. The most important thing currently to be resolved is to cause Koreans to look back on their own history in a freer way of thinking and with diverse, profound, and sharp insight, taking away the old and existing conventional recognition that is entangled with complicated interests with Korean people and other countries. The meanings of Chosun, Khori, and Solongos have been interpreted arbitrarily without any historic evidence by the scholars who followed conventional tradition of fixed-minded aristocrats in an agricultural society. If the Siberian cultural properties of the stone age, the earthenware age, the bronze age, and the iron age are analyzed in such a way, archaeological discovery will never be able to contribute to the restoration of the Koguryo's pastoral nomadic identity. One should transcend the errors that tend to interpret the cultural properties discovered in the pastoral nomadic regions as not being differentiated from those of agricultural regions and just interpret them altogether from the agricultural point of view. A more careful intention is required in the interpretation of cultural properties of ancient Korean empires that seem to have been formed due to mutual interactions of pastoral nomadic and agricultural cultures. Also, it is required that the conventional recognition chain of 'reverse-genes' be severed, which has placed more weight on agricultural properties than pastoral nomadic ones, since their settlement on agricultural farms was made after the establishment of their ancient pastoral nomadic empires. There is no reason at all to place priority on stoneware, earthenware, bronze ware, and iron ware than on wooden ware(木器) and other ware which were made of animal skins(皮器), bones and horns(骨角器), in analyzing the history in the regions of reindeer or sheep pastures. Reading ancient Korean history from the perspective of pastoral nomadic history, one feels strongly the instinctive emotions to return to the natural 'mother place'. The reindeer-herding pastoral nomadic identity of the Koguryo people that has been accumulated in volumes in their genes and hidden deep inside and have interacted organically could be reborn with Burqanism(Burqan refers to 不咸 in Chinese), which was their religion by birth and symbolized as the red willow(紅柳=不咸). The mother place of the Koguryo's people is the endless vast green pastures of North Eurasia and North America, where we anticipated the development of Korean livestock farming following the inherent properties in the genes of the reindeer-herding pastoral nomads with Korean ancestors. We anticipate that the place would be the core resource that could contribute to the development of life of living creatures following the inherent properties of their genes and biotechnological factors. In other words, biotechnology used for a search for clues on the well-being of humans could be the fruit brought by Burqanism of the Koguryo people and the fruit of the globalization of Korean livestock farming. It is the Chosun farmer in China come from the vast nomadic reindeer pastures of North Eurasia that resolved the food problem of a billion Chinese people with lowland paddy rice seeds (水稻) by transforming Heilongjiang Province(黑龍江省) into an oceanic lowland paddy rice field(水田). Even Mao Tse-tung(毛擇東) could not resolve the food problem by his revolution campaigns for tens of years. Today is the very time that requires the development of special livestock farming following the inherent properties of the ancient Korean reindeer-herding pastoral nomads that respected the dignity of life on the cold and dry plateau of North Eurasia and the America continent. I suggest that research should be started from the pastures of the Dariganga Steppe in East Mongolia that was the homeland of Hanwoo(韓牛) and the central horse-herding steppe place(牧馬場) of Chingis Khan's Mongolia. The Dariganga Steppe is awash with an affluent natural environment for pastoral nomadic living however, the quality of life of the pastoral nomads there is still low. I suggest we Koreans, the descendents of the Koguryo, should take our first steps for our livestock farming business project and develop the Northern nomadic pastures, here at the pastures of the Dariganga Steppe, which is the Mongolian core place of state-of-the-art technology for military weapons.
This experiment was conducted to investigate the effet of phthalimido-methyl-O,O-dimethyl-phosphorodithioate (Imidan) known as an acaricide and its possible metabolic products on the growth of plant, when sprayed on the leaves of rice plant. The results are summarized as follows. 1) Possible metabolic products of Imidan, the following compounds were synthesized or recrystallized for the present experiment a) N-Hydroxymethyl phthalimidem b) Phthalimide c) Phthalamidic acid d) Phthalic acid e) Anthranilic acid f) p-Amino benzoic acid g) p-Hydroxy benzoic acid h) Benzoic acid 2) Among the above materials, a), c), d), e), and Imidan were dissolved in a buffer solution respectively to be 10 and 20 p.p.m. and tested with the wheat coleoptile straight growth method. According to the results, Imidan inhibited the growth of coleoptile in both 10 and 20 p.p.m., whereas the others showed much better growth than the control, especially phthalamidic acid in 10 p.p.m. It appears that Imidan itself inhibits the coleoptile growth, whereas the metabolites derived from Imidan through various metabolisms, including hydrolysis in plant tissues show growth-regulating activity. (refer: Table 1, Fig. 1) 3) 20, 100 and 200 p.p.m. solutions of Imidall emulsion in xylene f·ere prepared. The lengths of shoot and root of rice seeds germinated on the re-respective media were measured after 12 days. The data showed that root was much more elongated in Imidan 20 p.p.m., whereas shoot in Imidan 100 p.p.m., respectively, than in the xylene control. An interesting finding was that xylene used as solvent had a tendency to inhibit seriously the root growth of rice seed. (refer: Table 2,5). 4) The emulsions of concentrations in 10, 25, 50 and 100 p.p.m's of control, Imidan, N-hydroxy methyl phthalimide, anthranilic acid, and phthalmide, respectively, were sprayed twice on the rice plant on pot. After a certain period of time lengths of rice culms were measured, showing that plots treated with Imidan and N-hydroxy methyl phthalimide exhibited much more growth than those of control and the others. 5) Loaves and stems of rice plant were sampled and extracted with dried acetone at the intervals of 3-, 5-, 7-, and 14 days after treated with Imidan 250 p.p.m. emulsion. This sample extracted with acetone was purified by means of prechromatographic purification method with acetonitrile and paperchromatographed to detect the following metabolic products. Imidan (Rf: 0.97-0,98), N-hydroxy-methyl phthalimide (Rf: 0.87) phthalimide (Rf: 0.86-0.87), phthalamidic acid (Rf: 0.13-0.14), phthalic acid (Rf: 0.02-0.03), benzoic acid (Rf: 0.42-0.43), p-amino benzoic acid or p-hydroxy benzoic acid (Rf: 0.08-0.09), and unidentified compounds (Rf: 0.73, 0.59, 0.33, 0.23. 0.07). In addition, in the early stages, such as 3- and 5 days nonhydrolyzed Imidan and its first hydrolytic product, N-hydroxymethyl phthalimide were detected in relatively large amounts, whereas in the last stages of 7- and 14 days due to further decomposition, the afore-mentioned two materials were reduced in the amount and p-hthalic, phthalamidic, benzoic, and p-Hydroxy benzoic, or p-Amino benzoic acids were detected in a considerably large amount. It is, therefore, believed that most of Imidan applied to the leaves of rice plant may be decomposed within almost 14 days. In the light of above observations it is considered that Imidan itself is not involved in plant growth regulating activity, whereas various phthaloyl derivatives produced in the course of metabolism (namelr, enzymic action) in plant tissues may have such effect.
The purpose of this paper was to review the results of the subjective well-being(swb) studies performed by Hahn and coworkers in Korean culture. As the correlates of swb, we dealt with demographic/individual difference variables, intrapersonal variables, interpersonal process variables, and Korean cultural variables. We proposed that the components of swb were consisted of quality of life(cognitive swb) and overall happy feelings about one's own life(emotional swb). It was also assumed that a measure of total swb could be calculated by summated mean of cognitive swb and emotional swb measures. The data of the swb studies were analyzed and interpreted according to the above three measures of swb. The results of a nationwide survey(Hahn, 2004) from age of 19 to 75 years ald(n=2,230) showed significant simple correlation coefficients between the following demographic/individual difference variables and swb: Gender difference in swb was found(total swb r=.08, p<.001; life satisfaction r=.10, p<.001; overall emotional swb r=.05, p<.05). Men were happier than women in terms of all three measures of swb. It was also found that women appeared to experience greater positive and negative emotions. Correlation between age and emotional swb(r=.09, p<.001) was significant, but life satisfaction was not significant(r=.04, n.s). Correlations between economic status and swb were also significant(total swb r =.23, p<.001; life satisfaction r=.15 p<.001; overall emotional swb r=.15, p<.001l). Although existence of father was negatively related to emotional swb(r=-.05, p<.05), the existence of mother was not related to any of swb measures. Similarly existence of brothers was related positively to overall emotional swb, but existence of sisters was not. Though existence of son was not related to swb, daughter contributed negatively to swb(total swb -.12, p<.01; life satisfaction -.09, p<.05; emotional swb r=-.12, p<.01). We assumed that family member-in-Iaw also contributed to swb because the extended dose social networks were important in Korean culture. The results showed that the following family member-in-law variables were related to swb: Parents-in-law(total swb r=.11, p<.01; life satisfaction r=.10, p<.01; emotional swb r=.10, p<.01), father-in-law(total swb r=.11, p<.01; life satisfaction r=.11, p<.01; emotional swb r=.06, n.s). The result suggested that especially father-in-law contributed to swb through financial and social support. Correlations between emotional experiences in everyday life and swb were also presented. The range of correlation coefficients between the positive emotion measures and swb were r=.30~.48(p<.001) when the above two measures obtained at same time. But the range decreased to r=.19~32(p<.001) when the swb measure was obtained 9 month later longitudinally. Intercorrelations between positive emotional experience; and life satisfaction were r=.37~58(p<.001) when two measures were obtained at same time. We also examined the effects of the intrapersonal cognitive responses to the most stressful life event upon swb. The results of nationwide survey(n=1,021) showed that self-disclosure(total swb r=.09, p<.010; life satisfaction r=.10, p<.01; emotional swb r=.07, p<.01), rumination(total swb r=-.17, p<.001), thought avoidance(total swb r=.12, p<.001; life satisfaction r=-.08; emotional swb r=-.12, p<.001) and suppression(total swb r=-.13, p<.001; life satisfaction r=-.08, p<.05: emotional swb r=-.13, p<.001) contributed to swb. It was also suggested that mismatch between self-guide and regulatory focus contributed negatively to emotional swb. It was also found that social comparison motives and fulfillment of the motives contributed to swb. The results of a survey research(n=363 college students) revealed that the higher the general social comparison motive, the lower the swb(total swb r=-.15, P<.01: life satisfaction r=-.17. p<.01; emotional swb r=-.10, p<.05). It was also found that satisfaction level of self-evalution motive contributed positively to swb(total swb r=-.14. p<.01: life satisfaction r=-.12, p<.05; emotional swb r=.15, p<.001). Both of self-improvement motive(r=.13, p<.05) and satisfaction level of self-improvement motive(r=.12, p<.05) contributed positively to emotional swb, respectively. The above results suggested that swb was depended upon the interaction effect of social comparison motive; and level of fulfillment of the motives. We also reported the significant multiple predictors of swb in a sample of age from 60years to 89years olds. The results of multiple regression analysis showed that the significant multiple predictors of swb were past illness(β=.174, p<.001), economic status(β=.418, p<.001), marital satisfaction(β=.0841, p<.001), satisfaction of offsprins(β=.065, p<.01), expectation level of social support from offsprings(β=-.049, p<.001), and negative emotions(β=-.454. p<.001) among 16 social psychological factors. It was also found that swb was an important multiple predictors of physical health. This finding was replicated in a longitudinal study. Both of positive and negative emotional experiences were significant multiple predictors of physical health one year later. The results of the discriminant analysis showed both of total swb and positive emotional experiences contributed to discriminate the happy and healthy olds from unhappy and unhealthy olds. We paper also examined the effects of the nonnative social behaviors upon swb in Korean culture. The main hypotheses of the study(Hahn, 2006, in press) was that the important nonnative behaviors would influence on swb through both of the mediation processes of adjustment to social relationships and psychological stress. The survey data were collected from 2,129 adults age of 19 to 75, from 7 regional areas in Korea. The results of the study revealed that almost all of correlation coefficients between 15 normative social behaviors and the above three criteria w-ere significant. The fitness test results of the covariance structural equation model showed that all of the fitness indices were satisfactory (GFI=.974, AGFI=.909, NNFI=.922, NFI=.973, CFI=.974. RMR=.049, RMSEA=.073). The results of the analysis revealed that the following five path coeffi6ents from behaviors to social adjustment were significant; behavior tor family and family members(t=5.87, p<.001), courteous behavior(t=4.39, p<.001), faithful behavior (t=2.15. p<.05). collectivistic behavior(t=8.31, p<.001). Seven path coefficients from the normative behaviors to psychological stress were significant; behavior for family and family members (t=-4.63, p<.001), faithful behavior(t=-3.86, p<.001). suppression of emotional expression(t=3.99, p<.001), trustworthy and dependable behavior(t=-2.21, p<.05), collectivistic behavior(t=3.72, p<.001), effortful and diligent behavior(t=2.94, p<.001), husbandry and saving behavior(t=3.40, p<.001). The above results suggested that four normative behaviors among seven behaviors contributed negatively to psychological stress in current Korean society. The results abo confirmed the hypothesized paths from social adjustment (t=10.40, p<.001) to swb and from psychological stress(t=-19.74, p<.001) to swb. The important results of the study were discussed in terms of the Confucian traditions and recent social changes in Korean culture. Finally limitations of this review paper were discussed and the suggestions for the future study were also proposed.
1. In order to investigate on the microflora and enzyme activity of mold wheat 'Nuruk' , the major source of microorganisms for the brewing of Takju (a Korean Sake), two samples of Nuruk, one prepared at the College of Agriculture, Chung Nam University (S) and the other perchased at a market (T), were taken for the study. The molds, aerobic bacteria, lactic acid bacteria, and yeasts were examined and counted. The yeasts were classified by the treatment with TTC (2, 3, 5 triphenyltetrazolium chloride) agar that yields a varied shade of color. The amylase and protease activities of Nuruk were measured. The results were as the followings. a) In the Nuruk S found were: Aspergillus oryzae group,