• Journal of The Korean Society of Inherited Metabolic disease
• /
• v.17 no.3
• /
• pp.96-102
• /
• 2017

Glycogen storage disease type IX (GSD IX) is caused by deficiency of phosphorylase kinase which plays a role in breakdown of glycogen. Mutations in PHKA2 are the most common cause of GSD IX (GSD IXa). Clinical manifestations of GSD IXa include hepatomegaly, elevation of liver enzyme, growth retardation, fasting hypoglycemia, and fasting ketosis. However, the symptoms overlap with those of other types of GSDs. Here, we report Korean familial cases with GSD IXa whose diagnosis was confirmed by targeted exome sequencing. A 4-year old male patient was presented with hepatomegaly and persistently elevated liver enzyme. Liver biopsy revealed swollen hepatocyte filled with glycogen storage, suggesting GSDs. Targeted exome sequencing was performed for the differential molecular diagnosis of various types of GSDs. A hemizygous mutation in PHKA2 were detected by targeted exome sequencing and confirmed by Sanger sequencing: c.3632C>T (p.Thr121Met), which was previously reported. The familial genetic analysis revealed that his mother was heterozygous carrier of c.3632C>T mutation and his 28-month old brother had hemizygous mutation. His brother also had hepatomegaly and elevated liver enzyme. The hypoglycemia was prevented by frequent meals with complex carbohydrate, as well as cornstarch supplements. Their growth and development is in normal range. We suggest that targeted exome sequencing could be a useful diagnostic tool for the genetically heterogeneous and clinically indistinguishable GSDs. A precise molecular diagnosis of GSD can provide appropriate therapy and genetic counseling for the family.

• Journal of Life Science
• /
• v.20 no.3
• /
• pp.457-461
• /
• 2010

Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant disorder characterized by reversible flaccid paralysis and intermittent hypokalemia. Although it has been reported that decreased activity in the $K_{ATP}$ channels of the skeletal muscle cell membrane plays a role in the pathogenesis of HOKPP, a clear mechanism has not yet been established. This study aimed to investigate the molecular biological mechanism underlying the decreased activity of $K_{ATP}$ channels in the skeletal muscles of familial HOKPP patients by studying the levels of the $K_{ATP}$ channel subunit Kir6.2. We found that when cells obtained from healthy individuals (normal cells) and HOKPP patients (patient cells) were treated with 4 mM potassium buffer, there was no quantitative change in the KCNJ11 mRNA levels and no difference in the Kir6.2 protein expression in the cytosol and cell membrane. On the other hand, when 1 mM potassium buffer was used, normal cells showed decreased expression of KCNJ11 mRNA as well as decreased expression of Kir6.2 protein in the cell membrane. However, patient cells treated with the same buffer showed no quantitative change in the levels of KCNJ11 mRNA or in the levels of Kir6.2 protein in the cytosol and cell membrane. Thus, in HOKPP patients, the Kir6.2 protein cannot be transported from the cell membrane to the cytosol, leading to closure of the $K_{ATP}$ channels, induction of depolarization, and subsequently, to the paralytic symptoms observed in the patient. Our findings thus provide new insights into the pathogenesis of HOKPP.

• Korea journal of population studies
• /
• v.33 no.2
• /
• pp.137-163
• /
• 2010

This study examines how individual, familial, and social factors are associated with persistent very low fertility in Busan Metropolitan City and contemplates family-friendly environments and social strategies for fertility increase. Fertility decline in Busan Metropolitan City recorded the lowest birth rate nationwide recent years among metropolitan cities and provinces in Korea. Birthrates are low partly because of multiple factors such as high age at childbearing and at marriage, decline in marriage, high divorce rate, the phenomena of marriage avoidance among unmarried women, traditional gender role attitude of men, low domestic work participation of husbands among dual career couples, low marital satisfaction and family life satisfaction, abortion, and more broader attiributes such as family policy, availability of childcare, education expenses, and family-friendlyness of a society. In addition, women of dual career couples in Busan strained from domestic work overload under traditional norms of gender role, and marital satisfaction recorded below average nationwide along with espeacially low marital satisfaction of wives compared to that of husbands. Major aspects of implications and considerations for higher birth rate and family friendly policy in Busan are discussed.

• Toxicological Research
• /
• v.14 no.2
• /
• pp.123-127
• /
• 1998

BRCA1 is a tumor suppresser gene in familial cases of breast cancer. It has been controversial whether the subcellular localization of BRCA1 is located in nuclei or cytoplasm in normal human breast cells. We found that a p220 protein was expressed in Type II Normal human breast epithelial cells (NHBEC) but not in Type I NHBEC in Western blot analysis using the 17F8 (3A2) antibody. Immunostaining using the same antibody revealed positive staining in nuclei, cytoplasm and perinuclei of Type II cells and negative staining in Type I NHBEC. The p220 protein, however, was expressed in SV40 immortalized Type I NHBEC and tumorigenic cells derived from them after x-ray and neu oncogene treatment. The subcelluar localization was mostly cytoplasmic and punctate in the nuclei. The breast carcinoma cell lines, MCF-7 and T47D, also expressed the p220 protein. Using RT-PCR, we observed the expression of BRCA1 mRNA in both Type I and Type II NHBEC. This result indicated that there might be mechanisms involved in post-translational or translational regulation of BRCA1 gene. It is speculated that the absence of BRCA1 protein expression in Type I NHBEC might playa role in their susceptibility to neoplastic transformation.

• Journal of Genetic Medicine
• /
• v.8 no.1
• /
• pp.17-27
• /
• 2011

Pre-eclampsia is a major cause of maternal and perinatal mortality and morbidity worldwide, but remains unclear about the underlying disease mechanisms. Pre-eclampsia is currently believed to be a two-stage disease. The first stage involves shallow cytotrophoblast invasion of maternal spiral arteriole, resulting in placental insufficiency. The hypoxic placenta release soluble factors, cytokines, and trophoblastic debris into maternal circulation, which induce systemic endothelial damage and dysfunction. This cause the second stage of the disease: maternal syndrome. Epidemiological research has consistently demonstrated a familial predisposition to pre-eclampsia. Intensive research efforts have been made to discover susceptibility genes that will inform our understanding of the pathophysiology of preeclampsia and that may provide direction for therapeutic or preventative strategies. In this review, we summarize the current understanding of the role of genetic factors in the pathophysiology of pre-eclampsia and explain the molecular approach to search for genetic clues in pre-eclampsia.

• Proceedings of the Korean Biophysical Society Conference
• /
• 2003.06a
• /
• pp.47-47
• /
• 2003

The presenilin 1 (PS1) or PS2 is an essential component of the ${\gamma}$-secretase complex, which mediates the intramembrane proteolysis of selected type-I membrane, including the ${\beta}$-amyloid precursor protein (APP) to yield A${\beta}$. Familial Alzheimer's disease (FAD)-associated mutations in presenilins give rise to an increased production of a highly amyloidogenic A${\beta}$42. In addition to their well-documented proteolytic function, the presenilins play a role in calcium signaling. We have previously reported that presenilin FAD mutations cause highly consistent alterations in intracellular calcium signaling pathways, which include deficits in capacitative calcium entry (CCE), the refilling mechanism for depleted internal calcium stores. However, molecular basis for the presenilin-mediated modulation of CCE remains to be elucidated. In the present study, whole-cell patch clamp method was used to identify a specific calcium-permeable ion channel current(s) that is responsible for the CCE deficits associated with FAD-linked PS1 mutants. Unexpectedly, both voltage-activated and conventional store depletion-activated calcium currents I(CRAC), were absent in HEK293 cells, which were stably transfected either with wild-type or FAD mutant (L286V, M146L, and delta E9) forms of PS1. Recently, magnesium-nucleotide-regulated metal cation current, or I(MagNum), has been described and appears to share many common properties with I(CRAC) including calcium permeability and inhibitor sensitivity (e.g. 2-APB). We have detected I(MagNum) in all 293 cells tested. Interestingly, FAD mutant 293 cells developed only about half of currents compared to PS1 wild type cells.

• Journal of Preventive Medicine and Public Health
• /
• v.49 no.3
• /
• pp.153-164
• /
• 2016

Objectives: Previous studies have obtained conflicting findings regarding possible associations between indices measuring carbohydrate intake and dyslipidemia, which is an established risk factor of coronary heart disease. In the present study, we examined crosssectional associations between carbohydrate indices, including the dietary glycemic index (GI), glycemic load (GL), total amount of carbohydrates, and the percentage of energy from carbohydrates, and a range of blood lipid parameters. Methods: This study included 1530 participants (554 men and 976 women) from 246 families within the Healthy Twin Study. We analyzed the associations using a generalized linear mixed model to control for familial relationships. Results: Levels of the Apo B were inversely associated with dietary GI, GL, and the amount of carbohydrate intake for men, but these relationships were not significant when fat-adjusted values of the carbohydrate indices were used. Triglyceride levels were positively associated with dietary GI and GL in women, and this pattern was more notable in overweight participants (body mass index [BMI] ${\geq}25kg/m^2$). However, total, low-density lipoprotein and high-density lipoprotein cholesterol levels were not significantly related with carbohydrate intake overall. Conclusions: Of the blood lipid parameters we investigated, only triglyceride levels were positively related with dietary carbohydrate indices among women participants in the Healthy Twin Study, with an interactive role observed for BMI. However, these associations were not observed in men, suggesting that the association between blood lipid levels and carbohydrate intake depends on the type of lipid, specific carbohydrate indices, gender, and BMI.

• Journal of Oriental Neuropsychiatry
• /
• v.22 no.3
• /
• pp.87-100
• /
• 2011

Objectives : Neurosis, psychosomatic disease from which most of out-patients suffer originated marital problem in clinical setting, In Oriental medicine, concept and clinical cases of the couple therapy is insufficient. So we suggest the theoretical background and evidence of oriental medical approach. Methods : We searched the theoretical perspectives of recent couple therapy and suggested the psychotherapy with couples in oriental medicine and its clinical utilization. Results : 1. Advantages of the couple therapy in oriental medicine were easy to relationship and emotional communication. because oriental medicine were available to approach of symptom pattern about somatic symptom due to marital problem. 2. Oriental medical therapy, for example, acupuncture, moxibustion, cupping, herbal medicine, etc. connects doctors and the patients easily, unlike dialogue-centered western psychotherapy. 3. The Ii-Gyeung-Byun-Qi Therapy(移精變氣療法) resolve the marital suppressed feeling easily, Gi-Un-Go-Roen Therapy (至言高論療法) is useful in four principle-marital role, communication, sex life, theory of Hwa-Byung. 4. The principle of 'sorrow restraints anger(悲勝怒)' and 'pleasure restraints sorrow(喜勝悲)' in Oh-Ji-Sang-Seung Therapy(五志相勝療法) accords with forgiveness and recovery that is ultimate goal of the couple therapy. Conclusions : Except existing therapy for recovery of marital relation, We suggest the somatic symptom centered approach based on mind and body unification in oriental medicine. This principle would bring the benefit from the marital to familial relation. From now on, we should correct the theory, need the theorical systematization. Then we should develop the program for recovery of marital relation and examine the hypothesis.

• Journal of Genetic Medicine
• /
• v.4 no.1
• /
• pp.1-5
• /
• 2007

Unprecedented amount of genetic information being generated from the result of Human Genome Project (HGP) and advances in genetic research is already forcing changes in the paradigm of health and disease. The ultimate goal of genetic medicine is to use genetic information and technology to develop new ways of treatment or even prevention of the disease on an individual level for 'personalized medicine'. Genetics is play ing an increasingly important role in the diagnosis, monitoring and management of common multifactorial diseases in addition to rare single-gene disorders. While wide range of genetic testing have provided benefits to patients and family, uncertainties surrounding test interpretation, the current lack of available medical options for the diseases, and risks for discrimination and social stigmatization may remain to be resolved. However an increasing number of genetic tests are becoming commercially available, including direct to consumer genetic testing, yet public is often unaw are of their clinical and social implications. The personal nature of information generated by a genetic test, its power to affect major life decisions and family members, and its potential misuse raise important ethical considerations. Therefore appropriate genetic counseling is needed for patient to be informed with the benefits, limitations and risks of genetic tests, prior to informed consent for the tests. Physician also should be familiar with the legal and ethical issues involved in genetic testing to tell patients how w ell a particular genetic risk factor relates with likelihood of disease, and be able to provide appropriate genetic counseling. Genetic counseling become a mandatory requirement as global standard for many genetic testing such as prenatal diagnosis, presymtomatic DNA diagnostic tests and cancer susceptibility gene test for familial cancer syndrome. In oder to meet the challenge of genetic medicine of 21 century in korean health care system, professional education program and certification board for medical genetics specialist including non-MD genetic counselors should be addressed by medical society and regulatory policy of national health insurance reimbursement for genetic counseling to be in place to promote the implementation of clinical genetic service including genetic counseling for proper genetic testing.

• Journal of Genetic Medicine
• /
• v.17 no.1
• /
• pp.27-33
• /
• 2020

Purpose: Duchenne muscular dystrophy (DMD) is the most common lethal muscular dystrophy and is caused by the genetic variants of DMD gene. Because DMD is X-linked recessive and shows familial aggregates, prenatal diagnosis is an important role in the management of DMD family. We present our experience of prenatal molecular diagnosis and carrier detection based on multiplex polymerase chain reaction (PCR), multiplex ligation-dependent probe amplification (MLPA), and linkage analysis. Materials and Methods: During study period, 34 cases of prenatal diagnosis and 21 cases of carrier detection were performed at the Seoul National University Hospital. Multiplex PCR and MLPA was used to detect the exon deletions or duplications. When the DMD pathogenic variant in the affected males is unknown and no DMD pathogenic variant is detected in atrisk females, linkage analysis was used. Results: The prenatal molecular diagnosis was offered to 34 fetuses. Twenty-five fetuses were male and 6 fetuses (24.0%) were affected. Remaining cases had no pathogenic mutation. We had 24 (80.0%) cases of known proband results; exon deletion mutation in 19 (79.2%) cases and duplication in 5 (20.8%) cases. Linkage analysis was performed in 4 cases in which 2 cases (50.0%) were found to be affected. In the carrier testing, among 21 cases including 15 cases of mother and 6 cases of female relative, 9 (42.9%) cases showed positive results and 12 (57.1%) cases showed negative results. Conclusion: Prenatal molecular diagnosis and carrier detection of DMD are effective and feasible. They are useful in genetic counseling for DMD families.