Purpose: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. Materials and Methods: Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). Results: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Although the KMT2B gene was identified as a causative gene for early-onset generalized dystonia, the efficacy of deep brain stimulation (DBS) in KMT2B-related dystonia has not been clearly elucidated. Here, we describe a 28-year-old woman who developed generalized dystonia with developmental delay, microcephaly, short stature, and cognitive decline. She was diagnosed with KMT2B- related dystonia using whole-exome sequencing with a heterozygous frameshift insertion of c.515dupC (p.T172fs) in the KMT2B gene. Oral medications and botulinum toxin injection were not effective. The dystonia markedly improved with bilateral pallidal DBS (the Burke-Fahn-Marsden Dystonia Rating Scale score was reduced from 30 to 5 on the dystonia movement scale and from 11 to 1 on the disability scale), and she could walk independently. From this case, we suggest that bilateral globus pallidus internus DBS can be an effective treatment option for patients with KMT2B-related generalized dystonia.

OBJECTIVE: The aim of this study was to investigate the efficacy of globus pallidus interna deep brain stimulation (GPi-DBS) for treating dystonia due to the GNAL mutation. METHODS: We provide the first report of a dystonia patient with a genetically confirmed GNAL mutation in the Korean population and reviewed the literature on patients with the GNAL mutation who underwent GPi-DBS. We compared the effectiveness of DBS in patients with the GNAL mutation compared to that in patients with DYT1 and DYT6 in a previous study. RESULTS: Patients with the GNAL mutation and those with DYT1 had higher early responder rates (GNAL, 5/5, 100%; DYT1, 7/7, 100%) than did patients with DYT6 (p = 0.047). The responder rates at late follow-up did not differ statistically among the three groups (p = 0.278). The decrease in the dystonia motor scale score in the GNAL group was 46.9% at early follow-up and 63.4% at late follow-up. CONCLUSION: GPi-DBS would be an effective treatment option for dystonia patients with the GNAL mutation who are resistant to medication or botulinum toxin treatment.
Botulinum Toxins ; Deep Brain Stimulation ; Dystonia ; Follow-Up Studies ; Globus Pallidus ; Humans

Grisel syndrome is a rare, non-traumatic atlanto-axial subluxation associated with an inflammatory or infectious process in the upper neck. According to the two-hit hypothesis, which is widely accepted for the pathogenesis of Grisel syndrome, preexisting ligamentous laxity of the atlanto-axial joint is regarded as the first hit. An inflammatory or infectious process of the atlanto-axial joint acts as the second hit, resulting in non-traumatic atlanto-axial subluxation. We report on a 6-year-old girl with atlanto-axial subluxation following retropharyngeal and cervical lymphadenitis. She was diagnosed with Grisel syndrome, for which an initial computed tomography did not show any preexisting ligamentous laxity of the atlanto-axial joint. A literature review found only 4 case reports on Grisel syndrome with an initially normal atlanto-axial joint. The present case offers some evidence that a single hit, such as inflammatory changes in the atlanto-axial joint, might cause Grisel syndrome, even without underlying ligamentous laxity.
Atlanto-Axial Joint* ; Child ; Female ; Humans ; Joint Instability ; Ligaments ; Lymphadenitis ; Neck ; Torticollis

OBJECTIVE: To identify the correlation between change in spinal deformities after surgical release and age at the time of surgery, and the effectiveness of surgical release in patients with neglected congenital muscular torticollis (CMT). METHODS: This was a retrospective study of 46 subjects with neglected CMT who had undergone surgical release at age ≥5 years at a tertiary medical center between January 2009 and January 2014. Spinal deformities were measured on anteroposterior plain radiographs of the cervical and whole spine, both preoperatively and postoperatively, to assess 3 parameters: cervicomandibular angle (CMA), lateral shift (LS), and Cobb angle (CA). We analyzed the change in spinal deformities after surgical release in consideration of age at the time of surgery. RESULTS: The median age at the time of surgery was 12.87 years. All 3 parameters showed significant improvement after surgical release (median values, pre- to post-surgery: CMA, 12.13° to 4.02°; LS, 18.13 mm to 13.55 mm; CA, 6.10° to 4.80°; all p<0.05). There was no significant correlation between age at the time of surgery and change in CMA (R=0.145, p=0.341) and LS (R=0.103, p=0.608). However, CA showed significant improvement with increasing age (R=0.150, p=0.046). CONCLUSION: We assessed the correlation between change in spinal deformities after surgical release and age at the time of surgery. We found that that surgical release is effective for spinal deformities, even in older patients. These findings enhance our understanding of the effectiveness and timing of surgical release in patients with neglected CMT.
Congenital Abnormalities ; Humans ; Retrospective Studies ; Spine ; Torticollis* ; Treatment Outcome

PURPOSE: Previous studies have revealed many inconsistent results regarding the relationship between vitamin D and metabolic syndrome. The purpose of our study was to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and factors that characterize metabolic syndrome in Korean children and adolescents. METHODS: We analyzed data from 2,880 children and adolescents aged 10-18 years collected from the 2008-2010 Korean National Health and Nutrition Examination Survey. We investigated the data according to quartiles of 25(OH)D concentrations. RESULTS: Systolic blood pressure and diastolic blood pressure with adjustment for sex and age differed significantly between the serum 25(OH)D groups and exhibited negative trend as 25(OH)D concentrations increased. The number of subjects with metabolic syndrome was greater in the low 25(OH)D groups (I, II, and III quartile) than in the high 25(OH)D group (IV quartile) (P=0.029). BMI and waist circumference were lower in the high 25(OH)D group. Serum 25(OH)D concentration correlated negatively with homeostasis model assessment estimate of insulin resistance (rho=-0.073, P<0.001) and correlated positively with quantitative insulin sensitivity check index (rho=0.095, P<0.001). CONCLUSION: Low serum 25(OH)D level is associated with an increase of insulin resistance and metabolic syndrome in children and adolescents.
Adolescent* ; Blood Pressure ; Child* ; Homeostasis ; Humans ; Insulin Resistance ; Nutrition Surveys* ; Obesity ; Vitamin D ; Waist Circumference

PURPOSE: Short stature is a very common reason for visits to pediatric endocrine clinics. It could be the first sign of an underlying disease. The purpose of this study is to investigate the etiologies and general characteristics of subjects who visited an outpatient clinic due to short stature. METHODS: We retrospectively reviewed the medical records of 3,371 patients who visited Severance Children's Hospital with the chief complaint of short stature from 2010 to 2012. Medical history, auxological data, and laboratory tests including bone age were collected and analyzed. Chromosome studies or combined pituitary function tests were performed if needed. RESULTS: Approximately 89.4% of the subjects with the chief complaint of short stature who visited the outpatient clinic were of normal height, and only 10.6% of subjects were identified as having short stature. Of the subject of short stature, 44.7% were classified as having normal variant short stature; that is, familial short stature (23.0%), constitutional delay in growth (17.7%), and mixed form (3.9%). Pathological short stature was found in 193 subjects (54.2%). Among pathological short stature, most common etiology was growth hormone deficiency (GHD) (38.9%). CONCLUSION: A majority of children had a normal height. Among children with short stature, pathological short stature and normal variants occupied a similar percentage. GHD was the most common cause of pathological short stature and found in about 20% of the children with short stature. In pathological short stature, the height, height velocity, and IGF-1 level were lower than in normal variants.
Ambulatory Care Facilities ; Child* ; Growth Hormone ; Humans ; Insulin-Like Growth Factor I ; Medical Records ; Pituitary Function Tests ; Retrospective Studies

beta-Glucosidase, which hydrolyzes cellobiose into two glucoses, plays an important role in the process of saccharification of the lignocellulosic biomass. In this study, we optimized the activity of beta-glucosidase of brown-rot fungus Fomitopsis pinicola KCTC 6208 using the response surface methodology (RSM) with various concentrations of glucose, yeast extract and ascorbic acid, which are the most significant nutrients for activity of beta-glucosidase. The highest activity of beta-glucosidase was achieved 3.02% of glucose, 4.35% of yeast extract, and 7.41% ascorbic acid where ascorbic acid was most effective. The maximum activity of beta-glucosidase predicted by the RSM was 15.34 U/mg, which was similar to the experimental value 14.90 U/mg at the 16th day of incubation. This optimized activity of beta-glucosidase was 23.6 times higher than the preliminary activity value, 0.63 U/mg, and was also much higher than previous values reported in other fungi strains. Therefore, a simplified medium supplemented with a cheap vitamin source, such as ascorbic acid, could be a cost effective mean of increasing beta-glucosidase activity.
Ascorbic Acid ; beta-Glucosidase* ; Biomass ; Cellobiose ; Coriolaceae* ; Fungi* ; Glucose ; Vitamins ; Yeasts

Congenital muscular torticollis (CMT) and craniosynostosis are diseases that cause plagiocephaly and craniofacial asymmetry in children. In our literature review, we did not find any report of concurrent manifestation of CMT and craniosynostosis. A 41-month-old boy visited our hospital with left torticollis, right laterocollis, and craniofacial asymmetry as the main findings. During clinical examination, prominent right sternocleidomastoid muscle and limited range of motion of the neck were noted, and right CMT was confirmed by magnetic resonance imaging of the neck. Three-dimensional computed tomography of the skull, which was conducted due to the unusual appearance of the skull with a large head circumference, mild brachycephaly, as well as left plagiocephaly, revealed premature closure of the sagittal suture. Thus, we report the first case that showed concurrence of CMT and sagittal synostosis. We recommend that concurrently manifested craniosynostosis needs to be examined if the subject with CMT displays unusual craniofacial asymmetry to a greater extent than deformational plagiocephaly.
Child ; Child, Preschool ; Craniosynostoses* ; Head ; Humans ; Magnetic Resonance Imaging ; Male ; Neck ; Plagiocephaly ; Plagiocephaly, Nonsynostotic ; Range of Motion, Articular ; Skull ; Sutures ; Torticollis*

PURPOSE: The rapid increase in the incidence of precocious puberty in Korea has clinical and social significance. Gonadotropin-releasing hormone (GnRH) stimulation test is required to diagnose central precocious puberty (CPP), however this test is expensive and time-consuming. This study aimed to identify factors that can predict a positive response to the GnRH stimulation test. METHODS: Clinical and laboratory parameters, including basal serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), were measured in 540 girls with clinical signs of CPP. RESULTS: Two hundred twenty-nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L (the CPP group). The CPP group had advanced bone age (P<0.001), accelerated yearly growth rate (P<0.001), increased basal levels of LH (P=0.02), FSH (P<0.001), E2 (P=0.001), and insulin-like growth factor-I levels (P<0.001) compared to the non-CPP group. In contrast, body weight (P<0.001) and body mass index (P<0.001) were lower in the CPP group. Although basal LH was significantly elevated in the CPP group compared to the non-CPP group, there was considerable overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L) detected CPP with 87.8% sensitivity and 20.9% specificity. CONCLUSION: No single parameter can predict a positive response on the GnRH stimulation test with both high sensitivity and specificity. Therefore, multiple factors should be considered in evaluation of sexual precocity when deciding the timing of the GnRH stimulation test.
Body Mass Index ; Body Weight ; Diagnosis ; Estradiol ; Female* ; Follicle Stimulating Hormone ; Forecasting ; Gonadotropin-Releasing Hormone* ; Humans ; Incidence ; Korea ; Luteinizing Hormone ; Puberty, Precocious*