Deep Phenotyping in 1p36 Deletion Syndrome

Youngkyu Shim,Young Jun Go,Soo Yeon Kim,Hunmin Kim,Hee Hwang,Jieun Choi,Byung Chan Lim,Ki Joong Kim,Jong-Hee Chae 대한소아신경학회 2020 대한소아신경학회지 Vol.28 No.4

Purpose: Although 1p36 deletion syndrome is the most common terminal deletion syndrome, unexplained phenotypic variability still occurs. We aimed to delineate the phenotype of this syndrome in detail and to characterize the phenotype-genotype correlation. Methods: We retrospectively reviewed 15 patients diagnosed with 1p36 deletion syndrome confirmed by chromosomal microarray. Results: All 15 patients revealed delayed attainment of motor milestones and speech. Seven patients (46.7%) never walked alone and only two (13.3%) could express a simple two-word sentence. They all showed subsequent intellectual disability. Two patients with large deletions of both distal and proximal critical regions of the 1p36 region shared severe intellectual disability with Rett syndrome-like behavioral features. Seizures, although frequent (73.3%), were well-controlled except in one patient with infantile spasms. Facial dysmorphism (92.9%) and ventricular mild dilatation with corpus callosum anomaly (46.7%) were common. Heart problems were identified in 14 patients, including structural abnormalities and/or functional problems associated with the gene encoding PR domain-containing protein 16. Two patients developed severe cardiac dysfunction requiring heart transplantation in their late teens. One patient with a 400 Kb deletion partly overlapping with the gene encoding calmodulin-binding transcription activator 1 did not have facial dysmorphism and presented with mild developmental delay and ataxic gait. One patient had a choledochal cyst, which was resected due to neonatal cholestasis. Conclusion: Although the phenotype of 1p36 deletion syndrome is quite consistent with previous reports, additional manifestations such as certain behavioral features, ataxic gait, and severe cardiac dysfunction at an early age should be considered.

국내 소아 뇌정맥혈전증의 임상적, 영상의학적 특징

심영규(Youngkyu Shim),김헌민(Hunmin Kim),황희(Hee Hwang),채종희(Jong-Hee Chae),최지은(Jieun Choi),김기중(Ki Joong Kim),임병찬(Byung Chan Lim) 대한소아신경학회 2018 대한소아신경학회지 Vol.25 No.4

목적: 뇌정맥혈전증(CVT)은 소아 뇌졸중의 드문 원인이며 다양한 임상양상과 임상의의 인식 부족으로 인해 진단 지연이 흔히 있을 수 있다. 본 연구에서는 단일 3차 어린이병원에 내원한 소아 뇌정맥혈전증 환자들의 임상적 특징에 대해 기술하고자 한다. 방법: 2000년부터 2016년까지 자기공명영상 또는 자기공명정맥조영술로 진단된 18세 이하 소아 뇌정맥혈전증 환자의 임상양상, 혈전이 생긴 부위, 치료, 결과 등에 대한 의무기록 자료를 후향적으로 분석하였다. 퇴원 시와 퇴원 후 3, 6, 12개월에 modified Rankin Scale(mRS) 을 사용하여 신경학적 예후를 평가하였다. 결과: 연구기간 동안 20명의 환자가 뇌정맥혈전증으로 진단되었다. 20명 중 14명은 남자 (14/20, 70%), 6명은 여자 (6/20, 30.0%) 였고 중간값 나이는 4세였다(생후 20일-17세). 가장 흔한 위험요인은 전신감염이었고(6/2, 30.0%) 12명의 환자가 첫 증상으로 두통과 구토를보였다(12/20, 60.0%). 처음 증상이 시작되고 48시간 동안 3명의 환자만이 경련을 보였으나 경과가 진행되면서 뇌영상을 찍게 되는 가장흔한 원인은 경련이었다(12/20, 60.0%). 증상 발생 후 진단 시까지 걸린 시간은 중간값으로 13일이었다(0-59일). 위시상정맥굴에 혈전이 발생하였을 경우 뇌내출혈 (4/11, 36.4%)과 임상적 경련 (9/11,81.8%)이 흔히 연관되었으며 항 혈전제 또는 항혈소판제 치료는 16명 (16/20, 80%)의 환자에서 투여되었다. 진단 후 3개월째 추적관찰에서 14명 환자 (14/20, 70%)의 mRS 는 0 또는 1 이었고, 이는 3분의 2 이상의 환자에서 신경학적 장애가 없었다는 것을 보여주었다. 결론: 경련과 뇌압상승 징후가 소아 뇌정맥혈전증에서 가장 흔한 임상 양상이었으나 진단 시 나이와 기저요인들을 포함한 임상적 특징들은 다양하였다. 진단 지연이 있음에도 불구하고 대부분의 환자에서 신경학적 예후는 양호하였다. Purpose: Cerebral venous thrombosis (CVT) is a rare cause of pediatric stroke. Our goal was to describe the clinical CVT features among pediatric patients presenting at a tertiary referral center. Methods: Patient data was retrospectively collected from the charts of all pediatric patients (newborn to 18 years old) who were diagnosed with CVT at Seoul National University Children’s Hospital between 2000 and 2016. Magnetic resonance imaging or venography was conducted for diagnostic confirmation. Modified Rankin Scale (mRS) was used to evaluate neurologic outcome. Results: Twenty patients were diagnosed with CVT during the study period (16 male, 4 female). Median age was 4 years. The most common risk factor was systemic infection (6/20, 30.0%). Twelve patients initially presented with headache or vomiting (12/20, 60.0%). Seizure was in only 3 patients within 48 hours of symptom onset; however, as the clinical course progressed, seizure was the symptom that most frequently led to brain imaging (12/20, 60.0%). Thrombosis in the superior sagittal sinus was frequently associated with intracranial hemorrhage (4/11, 36.4%) and clinical seizure (9/11, 81.8%). Anticoagulation and/or antiplatelet agents were used in 16 patients (16/20, 80%). At the 3-month follow-up, 14 patients (14/20, 70%) had an mRS of 0 or 1, showing that most of these patients had no neurologic impairment. Conclusion: Seizure and signs of increased intracranial pressure are the most common manifestation of pediatric CVT. However, clinical features are diverse and include age at symptom onset and underlying risk factors. Despite diagnostic delay, neurologic outcome is favorable in most patients.

Reading Single DNA with DNA Polymerase Followed by Atomic Force Microscopy

Kim, Youngkyu,Kim, Eung-Sam,Lee, Yoonhee,Kim, Joung-Hun,Shim, Bong Chu,Cho, Seong Moon,Lee, Jeong Soo,Park, Joon Won American Chemical Society 2014 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.136 No.39

<P>The importance of DNA sequencing in the life sciences and personalized medicine is continually increasing. Single-molecule sequencing methods have been developed to analyze DNA directly without the need for amplification. Here, we present a new approach to sequencing single DNA molecules using atomic force microscopy (AFM). In our approach, four surface-conjugated nucleotides were examined sequentially with a DNA polymerase-immobilized AFM tip. By observing the specific rupture events upon examination of a matching nucleotide, we could determine the template base bound in the polymerase’s active site. The subsequent incorporation of the complementary base in solution enabled the next base to be read. Additionally, we observed that the DNA polymerase could incorporate the surface-conjugated dGTP when the applied force was controlled by employing the force-clamp mode.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2014/jacsat.2014.136.issue-39/ja5063983/production/images/medium/ja-2014-063983_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja5063983'>ACS Electronic Supporting Info</A></P>

건축담론 - 건축, 기획의 시대

심영규,Shim, Youngkyu 대한건축사협회 2020 建築士 Vol.617 No.-

미래 전력시스템 변화에 따른 전력 수요자원시장의 방향성

심규한(Kyuhan Shim),고영규(Youngkyu Ko),신동일(Dong Il Shin) 대한전자공학회 2021 대한전자공학회 학술대회 Vol.2021 No.6

전력 수요관리 현황과 미래 수요관리 산업 전망

심규한(Kyuhan Shim),고영규(Youngkyu Ko) 대한전자공학회 2020 대한전자공학회 학술대회 Vol.2020 No.8

A familial case of limb-girdle muscular dystrophy with CAV3 mutation

Lee, Seungbok,Jang, Sesong,Shim, Youngkyu,Kim, Woo Joong,Kim, Soo Yeon,Cho, Anna,Kim, Hunmin,Kim, Jong-Il,Lim, Byung Chan,Hwang, Hee,Choi, Jieun,Kim, Ki Joong,Chae, Jong Hee Korean Society of Medical Genetics and Genomics 2019 대한의학유전학회지 Vol.16 No.2

Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies that has extremely heterogeneous clinical features and genetic background. The caveolin-3 gene (CAV3) is one of the causative genes. LGMD appears as a clinical continuum, from isolated skeletal muscle involvement to long QT syndrome. Here we report two patients without apparent muscle weakness in a family with CAV3 mutation. A 7-month-old Korean boy visited our muscle clinic because of an incidental finding of elevated serum creatine kinase (CK) concentration (680 IU/L, reference range, 20-270 IU/L) without clinical symptoms. The patient was born after an uneventful pregnancy and showed normal developmental milestones. He developed pseudohypertrophy of his calf muscle during the follow-up. We obtained a muscle biopsy at age 14 months, which showed size variations and degenerating/regenerating myofibers with endomysial fibrosis and immunohistochemical evidence of normal dystrophin. Under the impression of LGMD, we performed target panel sequencing and identified a heterozygous in-frame mutation of CAV3, c.307_312delGTGGTG (p.Val103_Val104del). Immunohistochemical staining of muscle indicated complete loss of caveolin-3 compared with normal control muscle, which supported the variant's pathogenicity. We performed segregation analysis and found that the patient's mother had the same variant with elevated serum CK level (972 IU/L). We report on autosomal dominant familial caveolinopathy caused by a pathogenic variant in CAV3, which was asymptomatic until the fourth decade. This case highlights the utility of next generation sequencing in the diagnosis of muscular dystrophies and the additive role of muscle biopsy to confirm the variants.

학문 목적 한국어 분야에서의 요구 분석 연구 동향 분석

조은영(Cho, Eunyoung),심윤진(Shim, Yunjin),안재린(Ahn, Jaerin),김영규(Kim, Youngkyu) 한국외국어교육학회 2012 Foreign languages education Vol.19 No.4

This paper presents a qualitative research synthesis of the studies on needs analysis in the field of Korean for academic purposes from 2003 to 2012. A total number of 47 research articles and theses/dissertations published during this period were classified and coded according to an analytic framework in terms of (1) types of analysis, (2) objects of analysis, (3) learner characteristics, (4) skills analysed, and (5) methods of analysis. The results show that (1) half of the studies took needs analysis as their main research topic, while the other half simply used needs analysis as one of their research methods; (2) the majority of the studies used questionnaires as their primary data collection method, and (3) the learner was the main object of analysis. The paper ends with suggestions for future research directions.

A familial case of limb-girdle muscular dystrophy with CAV3 mutation

Seungbok Lee,Sesong Jang,Youngkyu Shim,Woo Joong Kim,Soo Yeon Kim,Anna Cho,Hunmin Kim,Jong-Il Kim,Byung Chan Lim,Hee Hwang,Jieun Choi,Ki Joong Kim,Jong Hee Chae 대한의학유전학회 2019 대한의학유전학회지 Vol.16 No.2

Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies that has extremely heterogeneous clinical fea-tures and genetic background. The caveolin-3 gene (CAV3) is one of the causative genes. LGMD appears as a clinical contin-uum, from isolated skeletal muscle involvement to long QT syndrome. Here we report two patients without apparent muscle weakness in a family with CAV3 mutation.A 7-month-old Korean boy visited our muscle clinic because of an incidental ἀnding of elevated serum creatine kinase (CK) concentration (680 IU/L, reference range, 20-270 IU/L) without clinical symptoms. The patient was born after an uneventful pregnancy and showed normal developmental milestones. He developed pseudohypertrophy of his calf muscle during the follow-up. We obtained a muscle biopsy at age 14 months, which showed size variations and degenerating/regenerating myo-ἀbers with endomysial ἀbrosis and immunohistochemical evidence of normal dystrophin. Under the impression of LGMD, we performed target panel sequencing and identiἀed a heterozygous in-frame mutation of CAV3, c.307_312delGTGGTG (p.Val103_Val104del). Immunohistochemical staining of muscle indicated complete loss of caveolin-3 compared with normal control muscle, which supported the variant’s pathogenicity. We performed segregation analysis and found that the patient’s mother had the same variant with elevated serum CK level (972 IU/L). We report on autosomal dominant familial caveolinopathy caused by a pathogenic variant in CAV3, which was asymptom-atic until the fourth decade. This case highlights the utility of next generation sequencing in the diagnosis of muscular dystro-phies and the additive role of muscle biopsy to conἀrm the variants.

Hyperoxia-Induced ΔR ₁ : Magnetic Resonance Imaging Biomarker to Assess Cerebral Oxygenation and Ischemic Damage in Stroke

Suh, Ji-Yeon,Cho, Gyunggoo,Song, Youngkyu,Woo, Dong-Cheol,Choi, Yoon Seok,Ryu, Eun Kyung,Park, Bum Woo,Shim, Woo Hyun,Kim, Young Ro,Kim, Jeong Kon Ovid Technologies Wolters Kluwer -American Heart A 2018 Stroke Vol.49 No.12