• Journal of Genetic Medicine
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• v.7 no.1
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• pp.67-77
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• 2010

Purpose: The aims of this study are to evaluate psychological impact and quality of life according to the cancer diagnosis and mutation status in Korean families with BRCA mutations. Materials and Methods: Seventeen affected carriers (AC), 16 unaffected carriers (UC) and 13 healthy non carriers (NC) from 13 BRCA mutation families were included in the study. Outcomes were compared with regard to depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory, STAI), optimism (Reevaluation of the Life Orientation test, LOT-R), knowledge of hereditary ovarian cancer, and quality of life (QoL) (SF-36v2 Health Survey, physical component score [PCS], mental component score [MCS]) among three groups. Result: Level of depression, optimism, and PCS were similar in AC, UC, and NC. Anxiety score was elevated in all three groups. MCS was significantly low in AC than in UC and NC (P=0.009, P=0.017). Knowledge of hereditary breast and ovarian cancer was high in AC than NC (P=0.001). MCS was significantly related to whether patient was affected by cancer (P=0.043) and has occupation (P=0.008) or not in multivariable analysis. Conclusion: From this cross sectional study, psychological adverse effect was not related to the carrier status of BRCA mutation. Elevated anxiety in BRCA family members was observed but, independent to affection and the type of genetic mutation. AC showed low mental QoL. Further effort to understand psychological impact and QoL of genetic testing in BRCA family members is required for follow-up in clinical aspects.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.64-71
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• 2007

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.

• Journal of Genetic Medicine
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• v.4 no.2
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• pp.186-189
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• 2007

More than 6,000 rare disorders including genetic diseases have been reported. Of them, 1,500 diseases (1,211 for clinical diagnosis and 289 for research only) are technically possible for genetic testing. In Korea, since 2005, only 63 genetic diseases is permitted for prenatal genetic testing by the "Bioethics and Biosafety Law". The article 25 in the law prescribes 63 genetic diseases without clear indication for its selection and inclusion criteria. In EU, USA, and other foreign countries, however, there is no provision in the statute on prenatal genetic testing; it is not restricted by a law. Recently, a woman (Mrs. L, 38y) who is a carrier for Menkes disease made an appeal to a government for an amendment of the "Bioethics and Biosafety Law" prohibiting the prenatal diagnosis of her pregnancy at risk for Menkes disease. Menkes disease (MNK) is an X-linked recessive disorder characterized by neurodegeneration, connective tissue defects and hair abnormalities, and no effective treatment is available yet. The prevalence rate of MNK is one in about 250,000 live births. Menkes syndrome patients fail to absorb copper from the gastrointestinal tract in quantities adequate for meeting nutritional needs. These needs seem particularly acute during the initial 12 month of life, when the velocity of brain growth and motor neurodevelopment. Most of pts. die around 3yrs. of age. Mrs. L had a boy with Menkes disease who died at 2y.o. in 2001. Subsequent pregnancy in 2003, she was able to have prenatal genetic testing for mutation of the Menkes (ATP7A) gene and delivered a healthy baby boy. Now, She is pregnant again and wants to have prenatal diagnosis. however, this time, she was not allowed to have any more because Menkes disease is not included in 63 genetic diseases permitted by the law for prenatal genetic testing, in spite of the fact that she is a Menkes disease carrier and her pregnancy is at risk to have an affected baby. This case shows the practical problem of the legal restriction for prenatal genetic testing in Korea. In this study, we report a arguable case and discuss the controversial issues in the legal restriction for prenatal genetic testing in Korea.

• Journal of Genetic Medicine
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• v.4 no.2
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• pp.167-178
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• 2007

Purpose : The necessity of professional non-MD genetic counselor has been recently emphasized in a medical field. By conducting a national survey on the demands for generic counseling and professional non-MD generic counselor, we can make a long-term master plan to execute the educational program for professional genetic counselors and indeed promote genetic counseling in Korean health care service in a systemic manner. Methods : The survey has been conducted from September 3rd to October 4th of 2007 in a way of e-mail, telephone interview, fax, and direct contacts. It's targets were senior researchers and professors in medical and non-medical institutions, policy makers, research institutions or foundations. The survey questions consist of 16 questionnaires. Results : As a result of survey, 102 of 650 people responded. 80% of respondents indicated that genetic counseling is needed as a health care service and 34% among them considered it as "the most needed". In addition, 77% of the respondents showed that, it is necessary to have a professional non-MD genetic counselor with a master degree or higher in the field of medical genetics and among them 29% thought it as "the most necessary". A 77% of respondents considered that the cost of genetic counseling should be covered by health insurance and among them, 29% answered "strongly agreed". A 56% of respondents chose the answer of "They have a plan to hire the professional non-MD genetic counselor" in their institution, and among them 71% selected "within 5 years" in terms of when to hire. Also, they tend to expect the role of the professional non-MD genetic counselor to be not only "genetic counselor" (60%), but also "researcher" (42%), "educator" (18%) and "clinical laboratory coordinator" (19%). Conclusion : The 102 of 650 people responded to the survey. Based upon the nationwide survey over the needs on genetic counseling in health care service and demands on the professional non-MD genetic counselor, systematic educational program for the genetic counseling, with reimbursement coverage for counseling service by health insurance should be emphasized in development of a master plan.

• Journal of Genetic Medicine
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• v.5 no.1
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• pp.26-33
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• 2008

Purpose : Phenylketonuria(PKU) is an inborn error of metabolism and a genetic disorder resulting from a deficiency of phenylalanine hydroxylase(PAH) and decreased activity of tetrahydrobiopterin(BH4).In this study the correlation between the DNA mutation and clinical manifestations was investigated and PAH DNA mutations were compared bewteen Asian and Caucasian populations. Methods : DNA was isolated from peripheral leukocytes. The PAH gene was amplified by Polymerase Chain Reaction(PCR) and the sequence was analyzed with Multiplex Ligation-dependent Probe Amplification(MLPA). Results : We characterized the PAH gene of 102 independent Korean patients with PKU. PAH nucleotide sequence analysis revealed 44 different mutations, including 10 novel mutations comprising 9 missense mutations(N207D, K95del, A447P, G344D, P69S, S391I, A202T, G103S, and I306L) and 1 novel splice-site variant mutation(IVS10-3C>G). R243Q was the most prevalent mutation in this study. A259T has not previously been reported in Asian populations, but we found that this mutation had a frequency of 10.1% in our study. Furthermore, the genotypes of $BH_4$ responsive patients were analyzed and were divided into two groups: $BH_4$ medication-only group and $BH_4$ medication with diet therapy group. In the $BH_4$ medication-only group and $BH_4$ medication with diet therapy group, R241C was the most common mutation. Conclusion : Novel mutations in the PAH gene of PKU patients are still being discovered. Additional information as to the frequency of mutations in the tetrahydrobiopterine responsive gene is also accumulating. We anticipate that knowledge of these PKU gene mutations will assist the diagnosis, genetic counseling, and therapeutic treatment of PKU patients in future.

• Journal of Genetic Medicine
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• v.6 no.2
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• pp.175-178
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• 2009

The 22q11.2 duplication syndrome is an extremely variable disorder with a phenotype ranging from normal to congenital defects and learning disabilities. Recently, the detection rate of 22q11.2 duplication has been increased by molecular techniques, such as array CGH. In this study, we report a familial case of 22q11.2 duplication detected prenatally. Her first pregnancy was terminated because of 22q11.2 duplication detected incidentally by BAC array CGH. The case was referred due to second pregnancy with same 22q11.2 duplication. We perfomed repeat amniocentesis for karyotype and FISH analysis. Karyotype analysis from amniocytes and parental lymphocytes were normal, while FISH analysis of interphase cells presented a duplication of 22q11.2 in the fetus and phenotypically normal mother. The fetal ultrasound showed grossly normal finding. After genetic counseling about variable phenotype with intrafamilial variability with 50% recurrence rate, the couple decided to continue the pregnancy. The newborn had no apparent congenital abnormalities until 2 weeks after birth. We recommend that family members of patients with a 22q11.2 duplication be tested by the interphase FISH analysis. Also, we point out the importance of genetic counseling and an evaluation of the clinical relevance of diagnostic test results.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.11
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• pp.1653-1663
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• 2016

Meat quality is a complex trait influenced by many factors, including genetics, nutrition, feeding environment, animal handling, and their interactions. To elucidate relevant factors affecting pork quality associated with oxidative stress and muscle development, we analyzed protein expression in high quality longissimus dorsi muscles (HQLD) and low quality longissimus dorsi muscles (LQLD) from Duroc pigs by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis. Between HQLD (n = 20) and LQLD (n = 20) Duroc pigs, 24 differentially expressed proteins were identified by LC-MS/MS. A total of 10 and 14 proteins were highly expressed in HQLD and LQLD, respectively. The 24 proteins have putative functions in the following seven categories: catalytic activity (31%), ATPase activity (19%), oxidoreductase activity (13%), cytoskeletal protein binding (13%), actin binding (12%), calcium ion binding (6%), and structural constituent of muscle (6%). Silver-stained image analysis revealed significant differential expression of lactate dehydrogenase A (LDHA) between HQLD and LQLD Duroc pigs. LDHA was subjected to in vitro study of myogenesis under oxidative stress conditions and LDH activity assay to verification its role in oxidative stress. No significant difference of mRNA expression level of LDHA was found between normal and oxidative stress condition. However, LDH activity was significantly higher under oxidative stress condition than at normal condition using in vitro model of myogenesis. The highly expressed LDHA was positively correlated with LQLD. Moreover, LDHA activity increased by oxidative stress was reduced by antioxidant resveratrol. This paper emphasizes the importance of differential expression patterns of proteins and their interaction for the development of meat quality traits. Our proteome data provides valuable information on important factors which might aid in the regulation of muscle development and the improvement of meat quality in longissimus dorsi muscles of Duroc pigs under oxidative stress conditions.

• Journal of Food Hygiene and Safety
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• v.25 no.4
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• pp.388-394
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• 2010

Metabolomics aims at the comprehensive, qualitative and quantitative analysis of wide arrays of endogenous metabolites in biological samples. It has shown particular promise in the area of toxicology and drug development, functional genomics, system biology and clinical diagnosis. In this study, analytical technique of MS instrument with high resolution mass measurement, such as time-of-flight (TOF) was validated for the purpose of investigation of amino acids, sugars and fatty acids. Rat urine and serum samples were extracted by selected each solvent (50% acetonitrile, 100% acetonitrile, acetone, methanol, water, ether) extraction method. We determined the optimized liquid chromatography/time-of-flight mass spectrometry (LC/TOFMS) system and selected appropriated columns, mobile phases, fragment energy and collision energy, which could search 17 metabolites. The spectral data collected from LC/TOFMS were tested by ANOVA. Obtained with the use of LC/TOFMS technique, our results indicated that (1) MS and MS/MS parameters were optimized and most abundant product ion of each metabolite were selected to be monitorized; (2) with design of experiment analysis, methanol yielded the optimal extraction efficiency. Therefore, the results of this study are expected to be useful in the endogenous metabolite fields according to validated SOP for endogenous amino acids, sugars and fatty acids.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.194-199
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• 2008

Background: Early identification of pathogens can improve the prognosis of patients with ventilator associated pneumonia (VAP). In the present study, we evaluated the feasibility of performing multiplex PCR for endotracheal aspirates to detect three important pathogens (P. aeruginosa, K. pneumoniae and MRSA) in patients with VAP. Methods: The endotracheal aspirates of 24 patients were collected within 24 hours of the diagnosis of VAP for performing multiplex PCR. Forward and reverse primers were designed to target the specific site of each pathogen (the oprL gene for P. aeruginosa, 16S rRNA for K. pneumoniae and the mec gene for MRSA). We analyzed the clinical data of the VAP patients, including the culture reports for the endotracheal aspirates. Results: Twenty-four patients (M:F=18:6, mean age=$70{\pm}11$) with VAP were enrolled. Pathogens were isolated from 11 patients (P. aeruginosa in 2, K. pneumoniae in 1, MRSA in 2, other enteric Gram negative bacilli in 3, S. pneumoniae in 2 and mixed infection in 1). Multiplex PCR detected three cases of P.aeruginosa (2 cases coincided with the culture reports) and four cases of K. pneumoniae (1 matched with the culture report). PCR detected two MRSA cases, which did not coincide with the culture reports. Conclusion: Multiplex PCR of the endotracheal aspirate showed some ability to detect Gram negative bacilli, although caution is required when interpreting the results.

• Genomics & Informatics
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• v.9 no.2
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• pp.52-58
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• 2011

Osteoporotic fracture (OF), along with bone mineral density (BMD), is an important diagnostic parameter and a clinical predictive risk factor in the assessment of osteoporosis in the elderly population. However, a genome-wide association study (GWAS) on OF has not yet been clarified sufficiently. To identify OF-associated genetic variants and candidate genes, we conducted a GWAS in a population-based cohort (Korean Association Resource [KARE], n=1,427 [case: 288 and control: 1139]) and performed a de novo replication study in hospital-based individuals (Asan and Catholic Medical Center [ACMC], n=1,082 [case: 272 and control: 810]). In a combined meta-analysis, a newly identified genetic locus in an intergenic region at 10p11.2 (near genes FZD8 and ANKRD30A ) showed the most significant association (odd ratio [OR] = 2.00, 95% confidence interval [CI] = 1.47~2.74, p=$1.27{\times}10^{-6}$) in the same direction. We provide the first evidence for a common genetic variant influencing OF and genetic information for further investigation in bone metabolism.