المؤلفون: Heo, Jung, Lee, Sungjoo, Park, Jun, Yang, Heera, Park, Hyunju, Ki, Chang-Seok, Oh, Young Lyun, Kim, Hye In, Kim, Sun Wook, Chung, Jae Hoon, Kim, Kyunga, Kim, Tae Hyuk

المصدر: PLoS ONE; 11/10/2023, Vol. 18 Issue 11, p1-16, 16p

مصطلحات موضوعية: BRAF genes, THYROID cancer, TELOMERASE reverse transcriptase

مصطلحات جغرافية: SOUTH Korea

مستخلص: Background: Age at diagnosis (AAD) and telomerase reverse transcriptase (TERT) promoter mutations are prognostic factors in differentiated thyroid carcinoma (DTC), and the prevalence of the mutations increases with AAD. Considering this correlation, we investigated whether an interaction between AAD and the mutations is present and whether the mutation mediates the effect of AAD on the mortality rate in DTC. Methods: The study included 393 patients with DTC who were followed-up after thyroidectomy at a single medical center in Korea from 1994 to 2004. Multivariable Cox regression was used to investigate the interaction of AAD and TERT promoter mutation. Mediation analysis was conducted using a regression-based causal mediation model. Results: The age-associated mortality rate increased progressively in all DTC patients and wild-type TERT group (WT-TERT) with a linear trend (p < 0.001) contrary to mutant TERT group (M-TERT) (p = 0.301). Kaplan-Meier curves declined progressively with increasing AAD in the entire group, but the change was without significance in M-TERT. The effect of AAD on mortality was not significant (adjusted HR: 1.07, 95% CI 0.38–3.05) in M-TERT. An interaction between AAD and TERT promoter mutation (p = 0.005) was found in a multivariable Cox regression. TERT promoter mutations mediated the effect of AAD on the mortality rate by 36% in DTC in a mediation analysis. Conclusions: Considering the mediation of TERT promoter mutation on the effect of AAD on mortality, inclusion of TERT promoter mutation in a stage classification to achieve further individualized prediction in DTC is necessary. [ABSTRACT FROM AUTHOR]

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المؤلفون: Lee, Joon Hee, Song, Da Young, Jun, Sun-Hee, Song, Sang Hoon, Shin, Choong Ho, Ki, Chang-Seok, Lee, Kyunghoon, Song, Junghan

المصدر: PLoS ONE; 8/26/2020, Vol. 15 Issue 8, p1-12, 12p

مصطلحات موضوعية: PHYTOSTEROLS, HYPERCHOLESTEREMIA, CARDIOVASCULAR diseases, DIAGNOSTIC errors

مستخلص: Background: Sitosterolemia is an inherited lipid disorder which presents with elevated serum sitosterol and can result in an increased risk of premature cardiovascular disease. However, sitosterol cannot be accurately measured by routine diagnostic assays, meaning that sitosterolemia diagnosis can often be difficult, especially with many clinical features overlapping with familial hypercholesterolemia. With such complications resulting in increasing reports of misdiagnosis, the prevalence of sitosterolemia is predicted to be much higher than previously reported. Methods: Gas chromatography-mass spectrometry was utilized to measure sitosterol levels of normocholesterolemic and hypercholesterolemic children. Subsequently, an epidemiologically determined cutoff level of sitosterol was calculated and applied to estimate the prevalence of children with increased sitosterol and identify potential sitosterolemia patients. Massively parallel sequencing was used to confirm the diagnosis in suspected patients. Results: Samples from 109 normocholesterolemic and 220 hypercholesterolemic were tested for phytosterols. Sitosterol and campesterol levels were significantly increased in hypercholesterolemic children (mean 22.0±45.9 μmol/L for sitosterol and 26.0±32.8 μmol/L for campesterol) compared to normocholesterolemic children (mean 12.1±4.9 μmol/L for sistosterol and 14.8±6.7 μmol/L for campesterol). Via application of a cutoff of 35.9 μmol/L, the prevalence rates for increased and overtly increased sitosterol in hypercholesterolemic children were 6.4% and 1.4% respectively. Furthermore, 3 suspected sitosterolemia patients were identified, with 2 patients receiving molecular confirmation for sitosterolemia diagnosis. Conclusions: Our findings reaffirm that the prevalence of sitosterolemia is probably much higher than previously reported, which also indicates the significant risk of misdiagnosis of sitosterolemia with familial hypercholesterolemia. Special lipid testing including sitosterol, especially in children with uncontrolled hypercholesterolemia, is recommended in children in order to identify potential sitosterolemia patients that would otherwise be neglected. [ABSTRACT FROM AUTHOR]

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المؤلفون: Jang, Mi-Ae, Chung, Jong-Won, Yeon, Je Young, Kim, Jong-Soo, Hong, Seung Chyul, Bang, Oh Young, Ki, Chang-Seok

المصدر: PLoS ONE; 6/15/2017, Vol. 12 Issue 6, p1-9, 9p

مصطلحات موضوعية: MOYAMOYA disease, ARTERIAL stenosis, INTERNAL carotid artery, GENETIC disorders, TIME-of-flight mass spectrometry, MATRIX-assisted laser desorption-ionization, DISEASE risk factors

مستخلص: Purpose: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by stenosis of the internal carotid arteries with compensatory development of collateral vessels. Although a founder variant of RNF213, p.Arg4810Lys (c.14429G>A, rs112735431), is a major genetic risk factor for MMD in East Asians, the frequency and disease susceptibility of other variants in this gene remain largely unknown. In the present study, we investigated the association of RNF213 variants with MMD in Korean patients and population controls. Methods: For all RNF213 variants listed in the Human Gene Mutation Database (HGMD) as disease-causing or likely disease-causing mutations for MMD, genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Genetic data from 264 adult patients with MMD were analyzed and compared with two control populations comprised of 622 and 1,100 Korean individuals, respectively. Results: Among the 30 RNF213 variants that were listed in the HGMD, p.Arg4810Lys was identified in 67.4% (178/264) of patients with MMD and showed a significantly higher allele frequency than in the controls, giving an odds ratio of 63.29 (95% confidence interval, 33.11–120.98) for the 622 controls and 48.55 (95% confidence interval, 31.00–76.03) for the 1100 controls. One additional variant, p.Ala5021Val (c.15062C>T, rs138130613), was identified in 0.8% (2/264) of patients; however, the allele frequencies were not significantly different from those in the controls. Conclusions: These results suggest that, in our cohort of Korean patients, the p.Arg4810Lys is the only variant that is strongly associated with MMD among the 30 RNF213 variants listed in the HGMD. [ABSTRACT FROM AUTHOR]

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المؤلفون: Bang, Oh Young, Chung, Jong-Won, Cha, Jihoon, Lee, Mi Ji, Yeon, Je Young, Ki, Chang-Seok, Jeon, Pyoung, Kim, Jong-Soo, Hong, Seung Chyul

المصدر: PLoS ONE; 6/2/2016, Vol. 11 Issue 6, p1-9, 9p

مصطلحات موضوعية: ATHEROSCLEROSIS, GENETIC polymorphisms, MOYAMOYA disease, ANGIOGRAPHY, CAROTID body

مستخلص: Background: Both intracranial atherosclerotic stenosis (ICAS) and moyamoya disease (MMD) are prevalent in Asians. We hypothesized that the Ring Finger protein 213 gene polymorphism (RNF213), a susceptibility locus for MMD in East Asians, is also a susceptibility gene for ICAS in patients whose diagnosis had been confirmed by conventional angiography (absence of basal collaterals) and high-resolution MRI (HR-MRI, presence of plaque). Methods: We analyzed 532 consecutive patients with ischemic events in the middle cerebral artery (MCA) distribution and relevant stenotic lesion on the distal internal carotid artery or proximal MCA, but no demonstrable carotid or cardiac embolism sources. Additional angiography was performed on 370 (69.5%) patients and HR-MRI on 283 (53.2%) patients. Results: Based on angiographic and HR-MRI findings, 234 patients were diagnosed with ICAS and 288 with MMD. The RNF213 variant was observed in 50 (21.4%) ICAS patients and in 119 (69.1%) MMD patients. The variant was observed in 25.2% of patients with HR-MRI-confirmed ICAS. Similarly, 15.8% of ICAS patients in whom MMD was excluded by angiography had this variant. Among the ICAS patients, RNF213 variant carriers were younger and more likely to have a family history of MMD than non-carriers were. Multivariate testing showed that only the age of ICAS onset was independently associated with the RNF213 variant (odds ratio, 0.97; 95% CI, 0.944–0.99). Conclusions: RNF213 is a susceptibility gene not only for MMD but also for ICAS in East Asians. Further studies are needed on RNF213 variants in ICAS patients outside East Asian populations. [ABSTRACT FROM AUTHOR]

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المؤلفون: Moon, Seong Mi, Park, Hye Yun, Jeon, Kyeongman, Kim, Su-Young, Chung, Myung Jin, Huh, Hee Jae, Ki, Chang-Seok, Lee, Nam Yong, Shin, Sung Jae, Koh, Won-Jung

المصدر: PLoS ONE; 10/2/2015, Vol. 10 Issue 10, p1-12, 12p

مصطلحات موضوعية: MYCOBACTERIAL diseases, RESPIRATORY diseases, LUNG diseases, HEALTH outcome assessment, MEDICAL records, MEDICAL centers, PATIENTS

مستخلص: The clinical significance of Mycobacterium kansasii respiratory isolates is uncertain. The aims of this study were to determine the clinical relevance of M. kansasii isolates and to identify the clinical features and outcomes of M. kansasii lung disease. We reviewed the medical records of 104 patients from whom at least one respiratory M. kansasii isolate was obtained from January 2003 to July 2014 at Samsung Medical Center, South Korea. Of these 104 patients, 54 (52%) met the diagnostic criteria for nontuberculous mycobacterial lung disease; among them, 41 (76%) patients received antibiotic treatment for a median time of 15.0 months (interquartile range [IQR], 7.0–18.0 months). The remaining 13 (24%) without overt disease progression were observed for a median period of 24.0 months (IQR, 5.0–34.5 months). Patients with M. kansasii lung disease exhibited various radiographic findings of lung disease, including the fibrocavitary form (n = 24, 44%), the nodular bronchiectatic form (n = 17, 32%), and an unclassifiable form (n = 13, 24%). The fibrocavitary form was more common in patients who received treatment (n = 23, 56%), while the nodular bronchiectatic form was more common in patients with M. kansasii lung disease who did not receive treatment (n = 9, 70%). None of the patients with a single sputum isolate (n = 18) developed M. kansasii disease over a median follow-up period of 12.0 months (IQR, 4.0–26.5 months). In total, 52% of all patients with M. kansasii respiratory isolates exhibited clinically significant disease. Moreover, patients with M. kansasii lung disease displayed diverse radiographic findings in addition to the fibrocavitary form. The nodular bronchiectatic form was more common in patients with M. kansasii lung disease with an indolent clinical course. Thus, since the clinical significance of a single M. kansasii respiratory isolate is not definite, strict adherence to recommended diagnostic criteria is advised. [ABSTRACT FROM AUTHOR]

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المؤلفون: Bang, Oh Young, Ryoo, Sookyung, Kim, Suk Jae, Yoon, Chang Hyo, Cha, Jihoon, Yeon, Je Young, Kim, Keon Ha, Kim, Gyeong-Moon, Chung, Chin-Sang, Lee, Kwang Ho, Shin, Hyung Jin, Ki, Chang-Seok, Jeon, Pyoung, Kim, Jong-Soo, Hong, Seung Chyul

المصدر: PLoS ONE; Jun2015, Vol. 10 Issue 6, p1-10, 10p

مصطلحات موضوعية: MOYAMOYA disease, STENOSIS, ATHEROSCLEROSIS, STROKE patients, HEART disease diagnosis, ANGIOGRAPHY

مستخلص: Background: Both Moyamoya disease (MMD) and intracranial atherosclerotic stenosis (ICAS) are more prevalent in Asians than in Westerners. We hypothesized that a substantial proportion of patients with adult-onset MMD were misclassified as having ICAS, which may in part explain the high prevalence of intracranial atherosclerotic stroke in Asians. Method: We analyzed 352 consecutive patients with ischemic events within the MCA distribution and relevant intracranial arterial stenosis, but no demonstrable carotid or cardiac embolism sources. Conventional angiography was performed in 249 (70.7%) patients, and the remains underwent MRA. The occurrence of the c.14429G>A (p.Arg4810Lys) variant in ring finger protein 213 (RNF213) was analyzed. This gene was recently identified as a susceptibility gene for MMD in East Asians. Results: The p.Arg4810Lys variant was observed in half of patients with intracranial stenosis (176 of 352, 50.0%), in no healthy control subjects (n = 51), and in 3.2% of stroke control subjects (4 of 124 patients with other etiologies). The presence of basal collaterals, bilateral involvement on angiography, and absence of diabetes were independently associated with the presence of the RNF213 variant. Among 131 patients who met all three diagnostic criteria and were diagnosed with MMD, three-fourths (75.6%) had this variant. However, a significant proportion of patients who met two criteria (57.7%), one criterion (28.6%), or no criteria (20.0%) also had this variant. Some of them developed typical angiographic findings of MMD on follow-up angiography. Conclusions: Careful consideration of MMD is needed when diagnosing ICAS because differential therapeutic strategies are required for these diseases and due to the limitations of the current diagnostic criteria for MMD. [ABSTRACT FROM AUTHOR]

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المؤلفون: Oh, Seong-il, Park, Aram, Kim, Hee-Jin, Oh, Ki-Wook, Choi, Hojin, Kwon, Min-Jung, Ki, Chang-Seok, Kim, Hee-Tae, Kim, Seung Hyun

المصدر: PLoS ONE; Feb2014, Vol. 9 Issue 2, p1-9, 9p

مصطلحات موضوعية: MILD cognitive impairment, AMYOTROPHIC lateral sclerosis, GENETIC mutation, NEUROPSYCHOLOGY, KOREANS, NEUROPSYCHOLOGICAL tests, PROGNOSIS, PATIENTS, DISEASES

مستخلص: Background: Cognitive impairment is associated with a negative prognosis in amyotrophic lateral sclerosis (ALS), as well as with clinical specificity. We investigate neuropsychological function in ALS patients without known genetic mutations in a Korean tertiary clinic. Methods: Three hundred and eighteen patients were enrolled in a prospective longitudinal cohort from September 2008 to February 2012. At the time of diagnosis of sporadic ALS, we carried out genetic and comprehensive neuropsychological tests on all patients, and collected demographic and clinical characteristics. Six cognitive domains, namely executive function, attention, language, calculation, visuospatial function and memory were evaluated. ANOVA and t-tests were used to assess differences in clinical characteristics and neuropsychological parameters between sporadic ALS patients. The Kaplan-Meier method and Cox proportional hazard model were used for survival analysis. Results: One hundred and sixty-six patients were categorized into five subtypes: normal cognition (ALS pure), cognitive impairment (ALSci), behavioral impairment (ALSbi), frontotemporal dementia (ALS-FTD), and other types of dementia. Seventy patients (70/166, 42.2%) were cognitively or behaviorally impaired. Among the impaired patients, eight (8/166, 4.8%) had FTD-type dementia and one (1/166, 0.6%) was Alzheimer's disease-type. The ALS patients with cognitive impairment (ALSci) and with FTD (ALS-FTD) were more severely impaired in executive function, attention, language and memory than the cognitively intact ALS patients (ALS pure). In a survival analysis, ALSci (β = 1.925, p = 0.025) and ALS-FTD groups (β = 4.150, p = 0.019) tended to have shorter survival than the ALS pure group. Conclusions: About half of ALS patients without known genetic variation have cognitive or behavioral impairment. ALS patients with cognitive abnormalities, especially FTD, have a poorer prognosis than those without cognitive impairment. In neuropsychological profiling, executive tasks were effective in identifying cognitive impairment in the ALS patients. It would be useful for clinicians to classify ALS according to neuropsychological profiles, and screen for subtle cognitive impairment. [ABSTRACT FROM AUTHOR]

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المؤلفون: Kim, Hee-Jin, Won, Hong-Hee, Park, Kyoung-Jin, Hong, Sung Hwa, Ki, Chang-Seok, Cho, Sang Sun, Venselaar, Hanka, Vriend, Gert, Kim, Jong-Won

المصدر: PLoS ONE; Nov2013, Vol. 8 Issue 11, p1-7, 7p

مصطلحات موضوعية: SINGLE nucleotide polymorphisms, NUCLEOTIDE sequence, GENETIC mutation, HEARING disorders, GENETIC disorders, BIOINFORMATICS, ALLELES

مستخلص: Autosomal dominant non-syndromic hearing loss (AD-NSHL) is one of the most common genetic diseases in human and is well-known for the considerable genetic heterogeneity. In this study, we utilized whole exome sequencing (WES) and linkage analysis for direct genetic diagnosis in AD-NSHL. The Korean family had typical AD-NSHL running over 6 generations. Linkage analysis was performed by using genome-wide single nucleotide polymorphism (SNP) chip and pinpointed a genomic region on 5q31 with a significant linkage signal. Sequential filtering of variants obtained from WES, application of the linkage region, bioinformatic analyses, and Sanger sequencing validation identified a novel missense mutation Arg326Lys (c.977G>A) in the POU homeodomain of the POU4F3 gene as the candidate disease-causing mutation in the family. POU4F3 is a known disease gene causing AD-HSLH (DFNA15) described in 5 unrelated families until now each with a unique mutation. Arg326Lys was the first missense mutation affecting the 3^rd alpha helix of the POU homeodomain harboring a bipartite nuclear localization signal sequence. The phenotype findings in our family further supported previously noted intrafamilial and interfamilial variability of DFNA15. This study demonstrated that WES in combination with linkage analysis utilizing bi-allelic SNP markers successfully identified the disease locus and causative mutation in AD-NSHL. [ABSTRACT FROM AUTHOR]

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