• Journal of Genetic Medicine
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• v.7 no.2
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• pp.111-118
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• 2010

Chromosomal microarray analysis (CMA) enables the genome-wide detection of submicroscopic chromosomal imbalances with greater precision and accuracy. In most other countries, CMA is now a commonly used clinical diagnostic test, replacing conventional cytogenetics or targeted detection such as FISH or PCR-based methods. Recently, some consensus statements have proposed utilization of CMA as a first-line test in patients with multiple congenital anomalies not specific to a well-delineated genetic syndrome, developmental delay/intellectual disability, or autism spectrum disorders. CMA can be used as an adjunct to conventional cytogenetics to identify chromosomal abnormalities observed in G-banding analysis in constitutional or acquired cases, leading to a more accurate and comprehensive assessment of chromosomal aberrations. Although CMA has distinct advantages, there are several limitations, including its inability to detect balanced chromosomal rearrangements and low-level mosaicism, its interpretation of copy number variants of uncertain clinical significance, and significantly higher costs. For these reasons, CMA is not currently a replacement for conventional cytogenetics in prenatal diagnosis. In clinical applications of CMA, knowledge and experience based on genetics and cytogenetics are required for data analysis and interpretation, and appropriate follow-up with genetic counseling is recommended.

• Journal of Genetic Medicine
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• v.9 no.1
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• pp.42-46
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• 2012

Short-chain acyl-CoA dehydrogenase deficiency (SCADD; OMIM # 201470) is an autosomal recessive inborn error of mitochondrial fatty acid ${\beta}$-oxidation, presenting with a variety of clinical signs and symptoms. Developmental delay, hypertonia or hypotonia, ketotic hypoglycemia, and epilepsy are most frequently reported. In general, patients diagnosed through newborn screening have shown normal growth and development in contrast to those diagnosed as a result of clinically initiated evaluations. Here, the case of an asymptomatic Korean newborn with SCADD identified by tandem mass spectrometry is reported. The patient showed an elevated concentration of butyrylcarnitine detected on newborn screening. Urinary excretion of ethylmalonic acid was elevated by urine organic acid analysis. To confirm the diagnosis of SCADD, a direct sequencing analysis of 10 coding exons and the exon-intron boundaries of the ACADS gene were performed. Genetic analysis of ACADS showed the following novel compound heterozygous missense mutations: c.277C>A (p.Leu93Ile) on exon3 and c.682G>A (p.Glu288Lys) on exon6. These results will provide further evidence of mutational heterogeneity for SCADD.

• Stress
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• v.26 no.4
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• pp.259-267
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• 2018

Background: The purpose of this study was to identify the risk factors influencing cognitive function and life satisfaction in elderly living alone. Methods: It was cross-sectional descriptive study by using secondary data from the 2014 national survey of Korean elderly. The study sample consisted of 2,249 subjects who live alone, aged 65 years old and over. Data were analyzed frequency analysis, ${\chi}^2$-test, t-test, ANOVA and Logistic regression analysis. Results: The risk factors that significantly influenced cognitive function were old age, bereavement, lack of education, no regular exercise and low socio-cultural activity satisfaction. The risk factors that significantly influenced life satisfaction were no bereavement, lack of education, no work, negative evaluation of health status, diagnosis of depression and no regular exercise. Also experience of emotional and economical abuse, neglect of financial support and low cognitive function were identified risk factors of life satisfaction. Conclusions: The elderly living alone with risk factors of cognitive decline should be interested. To prevent or delay cognitive impairment, regular exercise and socio-cultural activities were recommended. It was suggested that the promotion of cognitive function, appropriate work and exercise, and social efforts to prevent abuse and neglect can contribute to improving life satisfaction of elderly living alone.

• Journal of Trauma and Injury
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• v.33 no.4
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• pp.227-235
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• 2020

Purpose: Alcohol intoxication is commonly associated with traumatic brain injury (TBI), but the influence of alcohol on the Glasgow Coma Scale (GCS) score remains unclear. This study investigates the effects of blood alcohol concentration (BAC) on the GCS score in head trauma patients with alcohol intoxication. Methods: In total, 369 head trauma patients with alcohol intoxication in a 1-year period were retrospectively analyzed. The patients underwent head computed tomography and had a BAC ≥80 mg/dL. Patients were divided into TBI and non-TBI groups. Brain injury severity was further classified using the head Abbreviated Injury Score (AIS). The effects according to 5 BAC groups were examined. Results: The TBI group consisted of 64 patients (16.2%). The mean BAC was significantly higher in the non-TBI group (293.4±87.3 mg/dL) than in the TBI group (242.8±89.9 mg/dL). The mean GCS score was significantly lower in the TBI group (10.3±4.6) than in the non-TBI group (13.0±2.5). A higher BAC showed a significant association with a lower mean GCS score in the TBI group, but not in the non-TBI group. Above ≥150 mg/dL, higher BACs showed significant odds ratios for a lower GCS score. Conclusions: The influence of alcohol in patients with head trauma depended on the presence of a brain injury. An association between a higher BAC and a lower GCS score was only observed in patients with TBI. Therefore, if a severe brain injury is suspected based on a GCS evaluation in patients with alcohol intoxication, prompt diagnosis and intensive care should be performed without delay.

• Health Policy and Management
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• v.32 no.1
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• pp.73-93
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• 2022

Background: Appropriate physician workforce projection through reasonable discussions and decisions with a broad view on supply and demand of the workforce, thus, is very important for high-quality healthcare services. The study expects to provide preliminary research data on the workforce diagnosis standard model for Korean physician workforce policy decision through more flexible and objective physician workforce projection in reflection of diverse changes in healthcare policy and sociodemographic environments. Methods: A low flow rate through the causal map was developed, and an objective workforce demand projection from 2019 to 2040 was conducted. In addition, projections by scenarios under various situations were conducted with the low flow rate developed in the study. Lastly, the demand projection of the physician workforce by region of 17 cities and provinces was conducted. Results: First, demand of physicians in 2019 was 110,665, 113,450 in 2020, 129,496 in 2025, 146,837 in 2030, 163,719 in 2035, and 179,288 in 2040. Second, the scenario for the retirement of baby boomers led to a decrease in the growth rate due to time delay. Third, Seoul and Gyeonggi-do account for a high percentage of demand, a very high upward trend was identified in Gyeonggi-do, and as a result, the projection showed that the demand of the physician workforce in Gyeonggi-do would worsen over time. Conclusion: This study is meaningful in that rational and collective physician workforce supply and demand and its imbalance in workforce distribution were verified through various projections by scenarios and regions of Korea with System Dynamics.

• The Journal of the Acoustical Society of Korea
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• v.41 no.5
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• pp.525-533
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• 2022

We propose an effective method for suppressing both side and grating lobes by applying 2-dimensional Fourier Transform to the received channel data during the receive focusing process of an ultrasound imaging system. When the signal from the image point is focused, the channel signals have the same DC value across the channels. However, even after echoes from outside an imaging point are focused, they are manifested as having different spatial frequencies depending on their incident angles. Therefore, after the receive focusing delay time is applied, 2-D Fourier Transform is performed on the time-channel data to separate the DC component and other frequency components in the spectral domain, and the weighting value is defined using the ratio of the two values. The side lobe and grating lobe were suppressed by multiplying the ultrasound image by a weighting value. Ultrasound images with a frequency of 5 MHz were simulated in a 64-channel linear array. The grating lobe appearing in the ultrasound image was completely removed by applying the proposed method. In addition, the side lobe was reduced and the lateral resolution was greatly increased. Results of computer simulation on a human organ mimicking image show that the proposed method can aid in better lesion diagnosis by increasing the image contrast.

• Tuberculosis and Respiratory Diseases
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• v.85 no.4
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• pp.349-357
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• 2022

Background: The most consistently identified mortality determinants for the new coronavirus 2019 (COVID-19) infection are aging, male sex, cardiovascular/respiratory diseases, and cancer. They were determined from heterogeneous cohorts that included patients with different disease severity and previous conditions. The main goal of this study was to determine if activities of daily living (ADL) dependence measured by Barthel's index could be a predictor for COVID-19 mortality. Methods: A prospective cohort study was performed with a consecutive sample of 340 COVID-19 patients representing patients from all over the northern region of Portugal from October 2020 to March 2021. Mortality risk factors were determined after controlling for demographics, ADL dependence, admission time, comorbidities, clinical manifestations, and delay-time for diagnosis. Central tendency measures were used to analyze continuous variables and absolute numbers (proportions) for categorical variables. For univariable analysis, we used t test, chi-square test, or Fisher exact test as appropriate (α=0.05). Multivariable analysis was performed using logistic regression. IBM SPSS version 27 statistical software was used for data analysis. Results: The cohort included 340 patients (55.3% females) with a mean age of 80.6±11.0 years. The mortality rate was 19.7%. Univariate analysis revealed that aging, ADL dependence, pneumonia, and dementia were associated with mortality and that dyslipidemia and obesity were associated with survival. In multivariable analysis, dyslipidemia (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.17-0.71) was independently associated with survival. Age ≥86 years (pooled OR, 2.239; 95% CI, 1.100-4.559), pneumonia (pooled OR, 3.00; 95% CI, 1.362-6.606), and ADL dependence (pooled OR, 6.296; 95% CI, 1.795-22.088) were significantly related to mortality (receiver operating characteristic area under the curve, 82.1%; p<0.001). Conclusion: ADL dependence, aging, and pneumonia are three main predictors for COVID-19 mortality in an elderly population.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.6
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• pp.441-452
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• 2022

Congenital diarrheal disorders (CDDs) with genetic etiology are uncommon hereditary intestinal diseases characterized by chronic, life-threatening, intractable watery diarrhea that starts in infancy. CDDs can be mechanistically divided into osmotic and secretory diarrhea. Congenital tufting enteropathy (CTE), also known as intestinal epithelial dysplasia, is a type of secretory CDD. CTE is a rare autosomal recessive enteropathy that presents with intractable neonatal-onset diarrhea, intestinal failure, severe malnutrition, and parenteral nutrition dependence. Villous atrophy of the intestinal epithelium, crypt hyperplasia, and irregularity of surface enterocytes are the specific pathological findings of CTE. The small intestine and occasionally the colonic mucosa include focal epithelial tufts. In 2008, Sivagnanam et al. discovered that mutations in the epithelial cell adhesion molecule (EpCAM, MIM# 185535) were the genetic cause of CTE (MIM# 613217). More than a hundred mutations have been reported to date. Furthermore, mutations in the serine peptidase inhibitor Kunitz type 2 (SPINT2, MIM# 605124) have been linked to syndromic CTE. In this study, we report the case of a 17-month-old male infant with congenital diarrhea. Despite extensive etiological workup, no etiology could be established before admission to our center. The patient died 15 hours after being admitted to our center in a metabolically decompensated state, probably due to a delay in admission and diagnosis. Molecular autopsy with exome sequencing revealed a previously reported homozygous missense variant, c.757G>A, in EpCAM, which was confirmed by histopathological examination.

• Journal of Genetic Medicine
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• v.19 no.2
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• pp.94-99
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• 2022

Lesch-Nyhan disease (LND) is a rare X-linked recessive inherited purine metabolic disorder that accompanies neurodevelopmental problems. Neurofibromatosis type 1 (NF1) is a relatively common autosomal dominant inherited genetic disorder characterized by tumors in various systems. Some children with NF1 also accompanies neurodevelopmental problems. Here, we describe a 5-year-old boy with a maternally inherited pathogenic variant in NF1 and hypoxanthine-guanine phosphoribosyltransferase (HPRT). He was referred for severe neurodevelopmental impairment and hyperuricemia. His mother was diagnosed with NF1 and the patient was also suspected of having NF1 because of cafe au lait macules. He had dystonia, rigidity, cognitive deficit, and speech/language impairment. Serum and urine uric acid concentrations were elevated. He had more severe neurodevelopmental delay than patients with only NF1, so his clinical symptoms could not be fully understood by the disease alone. To find the cause of his neurologic symptoms and hyperuricemia, the patient and his mother underwent a whole-exome sequencing test. As a result, the pathogenic variant c.151C>T (p.Arg51Ter) in HPRT1 was identified as hemizygote in the patient and heterozygote in his mother. The pathogenic variant c.7682C>G (p.Ser2561Ter) in NF-1 was identified as heterozygotes in both of them. Although the clinical symptoms of both diseases were overlapping and complicated, genetic testing was helpful for accurate diagnosis and treatment. Therefore, we suggest to consider preemptive genetic evaluation if there are symptoms not sufficiently explained by known existing diseases. And it is considered valuable to review this rare case to understand the clinical course and possible synergic effects of these diseases.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.77-85
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• 2022

The Td05 and Sgc8c, DNA-based aptamers, are well-known to target internalized surface markers (IGHM and PTK7) of Burkitt's lymphoma and acute lymphoblastic leukemia (ALL). Thus, Td05 and Sgc8c labeled with metallic radioisotope ⁶⁴Cu can be evaluated as potential diagnostic PET imaging agents. In this study, we modified the carbon chain length of the last adenosine of aptamer (n = 3, 6, 12) to increase tumor cell uptake and select the best candidate among six types of aptamer analogues and one adenosine of aptamer. After labeling of ⁶⁴Cu, [⁶⁴Cu]Cu-DOTA-aptamer analogues were evaluated in vitro studies (serum stability, Log P values, cell uptake, biodistribution). Then, we evaluate in vivo PET imaging study for two candidates (⁶⁴Cu-DOTA-C12-Sgc8c, ⁶⁴Cu-DOTA-C6-Td05). PET images clearly visualize tumors at 24 h post-injection rather than at an early time point and the tumor-to-background ratio also increases at the delay time point. ⁶⁴Cu-DOTA-C12-Sgc8c and ⁶⁴Cu-DOTA-C6-Td05 could be used as potential radiotracers for lymphoma.