Sporadic Hemiplegic Migraine Presenting ATP1A2 Mutation in Korea

Hemiplegic migraine (HM) is a rare form of migraine, characterized by migraine with reversible motor weakness. HM can be divided into sporadic and familiar HM based on familiarity. Mutations in CACNA1A, ATP1A2 and SCN1A were identified in familiar HM. We present a patient with sporadic HM exhibiting recurrent hemiplegia, mental change and fever along with headache attacks. During the hemiplegia, he showed perfusion delay in left middle cerebral artery territory. Genetic panel test revealed a likely pathogenic varia nt in ATP1A2.

Isolated Sphenoid Sinusitis withNontypeable Haemophilus influenzae Bacteremia in a Healthy Child

Acute bacterial sinusitis is one of the most common diseases in children, and 5–13% of patients with viral upper respiratory infection experience secondary bacterial sinusitis as a complication. Isolated sphenoid sinusitis is rarer than frontal, maxillary, and ethmoid sinusitis. However, it presents potentially devastating complications, such as cranial nerve involvement, brain abscess, and meningitis, owing to its anatomical location. Nontypeable Haemophilus influenzae (NTHi) commonly causes acute bacterial sinusitis but rarely causes bacteremia, particularly in immunocompetent patients. We present a rare case of a 14-year-old boy with bacteremia due to isolated sphenoid sinusitis caused by NTHi.

Genetic Analysis and Clinical Characteristics of Hereditary Pheochromocytoma and Paraganglioma Syndrome in Korean Population

Background@#Pheochromocytoma and paragangliomas (PPGL) are hereditary in approximately 30% to 40% cases. With the advancement of genetic analysis techniques, including next-generation sequencing (NGS), there were attempts to classify PPGL into molecular clusters. With NGS being applied to clinical settings recently, we aimed to review the results of genetic analysis, including NGS, and investigate the association with clinical characteristics in Korean PPGL patients. @*Methods@#We reviewed the medical records of PPGL patients who visited Severance hospital from 2006 to 2019. We documented the clinical phenotype of those who underwent targeted NGS or had known germline mutations of related genes. @*Results@#Among 57 PPGL patients, we found 28 pathogenic germline mutations of susceptibility genes. Before the targeted NGS was implemented, only obvious syndromic feature lead to the Sanger sequencing for the specific genes. Therefore, for the exact prevalence, only patients after the year 2017, when targeted NGS was added, were included (n=43). The positive germline mutations were found in 14 patients; thus, the incidence rate is 32.6%. Patients with germline mutations had a higher likelihood of family history. There were significant differences in the type of PPGLs, percentage of family history, metastasis rate, presence of other tumors, and biochemical profile among three molecular clusters: pseudohypoxic tricarboxylic acid cycle-related, pseudohypoxic von Hippel-Lindau (VHL)/endothelial PAS domain-containing protein 1-related, and kinase-signaling group. Germline mutations were identified in seven PPGL-related genes (SDHB, RET, VHL, NF1, MAX, SDHA, and SDHD). @*Conclusion@#We report the expected prevalence of germline mutations in Korean PPGL patients. NGS is a useful and accessible tool for genetic analysis in patients with PPGLs, and further research on molecular classification is needed for precise management.

Genetic Analysis and Clinical Characteristics of Hereditary Pheochromocytoma and Paraganglioma Syndrome in Korean Population

Background@#Pheochromocytoma and paragangliomas (PPGL) are hereditary in approximately 30% to 40% cases. With the advancement of genetic analysis techniques, including next-generation sequencing (NGS), there were attempts to classify PPGL into molecular clusters. With NGS being applied to clinical settings recently, we aimed to review the results of genetic analysis, including NGS, and investigate the association with clinical characteristics in Korean PPGL patients. @*Methods@#We reviewed the medical records of PPGL patients who visited Severance hospital from 2006 to 2019. We documented the clinical phenotype of those who underwent targeted NGS or had known germline mutations of related genes. @*Results@#Among 57 PPGL patients, we found 28 pathogenic germline mutations of susceptibility genes. Before the targeted NGS was implemented, only obvious syndromic feature lead to the Sanger sequencing for the specific genes. Therefore, for the exact prevalence, only patients after the year 2017, when targeted NGS was added, were included (n=43). The positive germline mutations were found in 14 patients; thus, the incidence rate is 32.6%. Patients with germline mutations had a higher likelihood of family history. There were significant differences in the type of PPGLs, percentage of family history, metastasis rate, presence of other tumors, and biochemical profile among three molecular clusters: pseudohypoxic tricarboxylic acid cycle-related, pseudohypoxic von Hippel-Lindau (VHL)/endothelial PAS domain-containing protein 1-related, and kinase-signaling group. Germline mutations were identified in seven PPGL-related genes (SDHB, RET, VHL, NF1, MAX, SDHA, and SDHD). @*Conclusion@#We report the expected prevalence of germline mutations in Korean PPGL patients. NGS is a useful and accessible tool for genetic analysis in patients with PPGLs, and further research on molecular classification is needed for precise management.

Performance of HemosIL ReadiPlasTin, a Liquid Reagent for Prothrombin Time Measurement / 임상검사와정도관리

BACKGROUND: Prothrombin time (PT) measurement is an important test for screening blood coagulation disorders and monitoring anticoagulant therapy. In this study, we evaluated the analytical performance of HemosIL ReadiPlasTin (Instrumentation Laboratory, USA), a liquid reagent for PT measurement. METHODS: The precision of HemosIL ReadiPlasTin was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) EP5-A3 guidelines. Further, comparison with HemosIL RecombiPlasTin 2G (Instrumentation Laboratory, USA) was made according to the CLSI EP9-A3 guidelines. The reference intervals were established according to the CLSI C28-A3 guidelines. RESULTS: The coefficient of variation values for repeatability and total imprecision at two levels of control materials were lower than 1.1% and 3.4%, respectively. The performance of HemosIL ReadiPlasTin was comparable to that of HemosIL RecombiPlasTin 2G, with a high correlation (r=0.996). The reference interval for normal subjects was 10.4–13.3 seconds. CONCLUSIONS: HemosIL ReadiPlasTin showed an acceptable degree of imprecision and its performance showed high correlation with that of a conventional reagent. Therefore, it is expected to be useful for PT measurement in clinical laboratories.

Evaluation of the Real-Q RV Detection Kit for the Identification of Viruses That Result in Respiratory Infections

Viral respiratory infections are one of the most common infections worldwide. It is important to detect the virus early and precisely. In this study, we evaluated the limit of detection (LoD) and usefulness of the Real-Q RV Detection kit (BioSewoom, Seoul, Korea). We measured the LoD of the Real-Q RV Detection kit using 10 strains of standard viruses. We then compared the detection results by the Allplex Respiratory Panel Assay kit (Seegene, Seoul, Korea) using 123 clinical specimens. The discrepant results were confirmed by sequencing. Among the 10 standard viruses, the LoD of human rhinovirus (HRV) was the lowest and that of parainfluenza virus 2 and 3 was relatively high as detected by Real-Q RV Detection kit. Agreements of the two kits ranged from 95.9% to 100%. Three specimens detected negative by the Allplex Respiratory Panel kit were detected as adenovirus (AdV) by the Real-Q RV Detection kit and were confirmed by sequencing. Similarly, a specimen detected negative by the Allplex Respiratory Panel kit was detected as HRV by the Real-Q RV Detection kit and was confirmed by sequencing. A specimen detected as human enterovirus by the Allplex Respiratory Panel kit was detected as HRV by the Real-Q RV Detection kit and was confirmed by sequencing. Real-Q RV Detection kit showed good diagnostic performance and can be useful for detecting major viruses that cause respiratory infections.

Deletion of 20p13 and Duplication of 20p13p12.3 in a Patient with Delayed Speech and Development

No abstract available.

Report on the External Quality Assessment Scheme for Cytogenetics and Molecular Cytogenetics in Korea (2016–2017)

In both 2016 and 2017, the cytogenetic and molecular cytogenetic programs conducted three assessments for the Korean Association of External Quality Assessment Service. A total of six cases with chromosomal aberrations were distributed in 2016, and nine cases were examined in 2017 in the chromosome surveys. For the fluorescence in situ hybridization surveys, six cases and nine cases were assessed in 2016 and 2017, respectively. A total of 38 laboratories in 2016 and 39 laboratories in 2017 participated in the cytogenetics program. In the molecular cytogenetics program, a total of 32 laboratories participated in 2016, and 31 laboratories participated in 2017. Most of the participating laboratories showed acceptable results for the cytogenetics and molecular cytogenetics programs. For the unacceptable results, there were various annotation errors, suggesting the need for continuous education and quality control.

Detection of Immunoglobulin Heavy Chain Gene Clonality by Next-Generation Sequencing for Minimal Residual Disease Monitoring in B-Lymphoblastic Leukemia

Minimal residual disease (MRD) following B-lymphoblastic leukemia (B-ALL) treatment has gained prognostic importance. Clonal immunoglobulin heavy chain (IGH) gene rearrangement is a useful follow-up marker in B-ALL owing to its high positivity rate. We evaluated the performance and clinical applicability of a next-generation sequencing (NGS) assay for IGH rearrangement in B-ALL MRD monitoring. IGH rearrangement was tested by using fluorescence PCR-fragment analysis and the NGS assay in eight B-ALL patients. The NGS assay was run on two platforms: the Ion Torrent PGM (Thermo Fisher Scientific, USA) (18 samples from 1st to 7th patients) and the MiSeq system (Illumina, USA) (four samples from 8th patient). All initial diagnostic samples and four follow-up samples were positive for clonal IGH rearrangement with fluorescence PCR-fragment analysis and the NGS assay, and six follow-up samples were positive only with NGS. In one case with BCR-ABL1 translocation, BCR-ABL1 quantitative PCR was negative but the NGS IGH assay was positive just prior to full-blown relapse, suggesting the high sensitivity and clinical utility of the NGS assay. The NGS assay is proposed for MRD monitoring in B-ALL Additional studies are needed to confirm the clinical implications of cases showing positive results only in NGS.

Concomitant AID Expression and BCL7A Loss Associates With Accelerated Phase Progression and Imatinib Resistance in Chronic Myeloid Leukemia

No abstract available.

Carbapenem Inactivation Method: Accurate Detection and Easy Interpretation of Carbapenemase Production in Enterobacteriaceae and Pseudomonas spp / 대한임상미생물학회지

BACKGROUND: We evaluated the carbapenem inactivation method (CIM) compared with the modified Hodge test (MHT) for the detection of carbapenemase-producing Gram-negative bacilli. METHODS: A total of 61 isolates of carbapenemase-producing Enterobacteriaceae (CPE: 14 KPC, 7 GES-5, 8 NDM-1, 9 VIM-2, 9 IMP-1, and 14 OXA-48-like), 34 isolates of metallo-β-lactamase (MBL)-producing Pseudomonas spp. (14 VIM-2 and 20 IMP-6), and 70 carbapenem-nonsusceptible carbapenemase-negative isolates were included. The CIM and MHT were performed for all of the isolates. To perform the CIM, a meropenem disk was incubated with a suspension of the isolate to be tested and then on Mueller-Hinton agar with the Escherichia coli ATCC 29522 strains. The absence of an inhibition zone indicates presence of a carbapenemase. The presence of a clearing zone indicates lack of a carbapenemase. RESULTS: The total sensitivity and specificity of CIM (96% sensitivity and 100% specificity) in carbapenem-nonsusceptible Enterobacteriaceae and Pseudomonas spp. were better than those of the MHT (77% sensitivity and 94% specificity). The interpretation of CIM results was easy, with no or 20 mm inhibition zones indicating negative carbapenemase activity. CONCLUSION: The CIM had excellent sensitivity and specificity for detection of CPE and MBL-producing Pseudomonas spp., and a positive result was easily determined, unlike the MHT.

PRSS1, SPINK1, CFTR, and CTRC Pathogenic Variants in Korean Patients With Idiopathic Pancreatitis

BACKGROUND: This study aimed to identify pathogenic variants of PRSS1, SPINK1, CFTR, and CTRC genes in Korean patients with idiopathic pancreatitis. METHODS: The study population consisted of 116 Korean subjects (65 males, 51 females; mean age, 30.4 yr, range, 1-88 yr) diagnosed with idiopathic chronic pancreatitis (ICP), idiopathic recurrent acute pancreatitis (IRAP), or idiopathic acute pancreatitis (IAP). We analyzed sequences of targeted regions in the PRSS1, SPINK1, CFTR, and CTRC genes, copy numbers of PRSS1 and SPINK1, and clinical data from medical records. RESULTS: We identified three types of pathogenic PRSS1 variants in 11 patients, including p.N29I (n=1), p.R122H (n=1), and p.G208A (n=9). Sixteen patients exhibited heterozygous pathogenic variants of SPINK1, including c.194+2T>C (n=12), p.N34S (n=3), and a novel pathogenic splicing variation c.194+1G>A. A heterozygous CFTR p.Q1352H pathogenic variant was detected in eight patients. One patient carried a heterozygous CTRC p.P249L pathogenic variant, which is a known high-risk variant for pancreatitis. All patients had normal PRSS1 and SPINK1 gene copy numbers. Weight loss occurred more frequently in patients carrying the p.G208A pathogenic variant, while pancreatic duct stones occurred more frequently in patients with the c.194+2T>C pathogenic variant. CONCLUSIONS: Pathogenic variants of PRSS1, SPINK1, and CFTR were associated with idiopathic pancreatitis, while pathogenic variants of CTRC were not. Copy number variations of PRSS1 and SPINK1 were not detected.

Isolated 9p Duplication With der(Y)t(Y;9)(q12;p13.2) in a Male Patient With Cardiac Defect and Mental Retardation Confirmed by Chromosomal Microarray

No abstract available.

An 18.3-Mb Duplication on Chromosome 14q With Multiple Cardiac Anomalies and Clubfoot Was Identified by Microarray Analysis

No abstract available.

Chronic Myeloid Leukemia With Rare Variant b2a3 (e13a3) BCR-ABL1 Fusion

No abstract available.

t(12;17)(p13;q12)/TAF15-ZNF384 Rearrangement in Acute Lymphoblastic Leukemia

No abstract available.

A Case Report of Anti-f(ce) Identified in a Patient with Pancreatic Cancer / 대한수혈학회지

Anti-f(ce) is a rare unexpected antibody against the ce(f) antigen. The aim of this study is to report a second case of anti-f(ce) identified in a patient. A 66-year-old-male with pancreatic cancer received percutaneous transhepatic biliary drainage. During pretransfusion tests, anti-f(ce) was identified. He had a history of multiple transfusions and was transfused with 2 units of antiglobulin crossmatch compatible RBCs without any adverse reactions. To confirm that the antibody was specific for ce(f) antigen, we crossmatched the patient's serum with RhD-positive red cells of Rh phenotype DcE, DCcEe, DCce, and DCe; all results were negative. Conversely, a crossmatch with RhD-negative red cells of Rh phenotype ce, Cce, and cEe, showed positive results for Rh phenotype ce and cEe red cells. Among the four reports that confirmed anti-e, we discovered the possibility of co-existence of anti-C or misidentification of anti-Ce as anti-e. Therefore, when antibodies against Rh antigens are identified, the possibility of co-existence of antibodies against compound antigens should be considered. Using unexpected antibody identification panel that ce(f) antigen positive red cells are marked is recommended for sensitive detection of anti-f(ce).

Prevalence and Molecular Characteristics of Carbapenemase-Producing Enterobacteriaceae From Five Hospitals in Korea

BACKGROUND: The emergence of carbapenemase-producing Enterobacteriaceae (CPE) represents a major clinical problem because these bacteria are resistant to most antibiotics. CPE remain relatively uncommon in Korea. We report the prevalence, clinical characteristics, and molecular epidemiology of CPE isolates collected from five university hospitals in Korea. METHODS: Between January and December 2015, 393 non-duplicated isolates that were nonsusceptible to ertapenem were analyzed. Production of carbapenemase, extended-spectrum β-lactamase, and AmpC β-lactamase was determined by genotypic tests. Antimicrobial susceptibility profiles were determined by using an Etest. Clonality of Klebsiella pneumoniae carbapenemase (KPC)-2-producing and oxacillinase (OXA)-232-producing Klebsiella pneumoniae isolates was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Of the 393 isolates tested, 79 (20.1%) were CPE. Of these 79 isolates, 47 (59.5%) harbored the bla(OXA-232) gene while the remaining isolates carried genes bla(KPC-2) (n=27), bla(IMP-1) (n=4), and bla(NDM-1) (n=1). Among the 24 KPC-2 K. pneumoniae isolates from hospital B, 100% were resistant to carbapenems, 8% to colistin, and 0% to tigecycline. Among the 45 OXA-232 K. pneumoniae at hospital C, 95% were resistant to ertapenem, 68% to imipenem, 95% to meropenem, 10% to colistin, and 24% to tigecycline. PFGE analysis revealed a unique pattern for KPC-2 K. pneumoniae and identified 30 isolates belonging to the dominant pulsotypes (PT)1 and PT2 among 41 OXA-232 K. pneumoniae isolates. CONCLUSIONS: CPE strains are present in Korea, with the majority of K. pneumoniae isolates producing OXA-232 and KPC-2. The prevalence and predominant genotypes of CPE show hospital-specific differences.

Frequency and Clinical Characteristics of Intrachromosomal Amplification of Chromosome 21 in Korean Childhood B-lineage Acute Lymphoblastic Leukemia

BACKGROUND: Intrachromosomal amplification of chromosome 21 (iAMP21) is known to be associated with poor prognosis in B-cell ALL (B-ALL). To determine the frequency and clinical characteristics of iAMP21 in Korean B-ALL patients, we performed FISH and multiplex ligation-dependent probe amplification (MLPA) analyses. METHODS: A total of 102 childhood B-ALL patients were screened with ETV6-RUNX1 FISH probes (Abbott Molecular, USA). The presence of an iAMP21 was confirmed by using MLPA P327 iAMP21-ERG probemix (MRC Holland, The Netherlands). RESULTS: iAMP21 was detected in one of the screened B-ALL patients (1/102 patients, 1.0%) who presented the ALL immunophenotype and complex karyotype at initial diagnosis. The patient relapsed twice after bone marrow transplantation. MLPA showed 12.5-Mb and 4.28-Mb regions of amplification and deletion, respectively. CONCLUSIONS: The frequency of iAMP21 is considerable in Korean pediatric patients. Our report suggests that iAMP21 in childhood B-ALL has very unfavorable impact on patient's prognosis. Additional methods such as MLPA analysis is essential to rule out patients with equivocal interphase FISH results.

Routine Chromosomal Microarray Analysis is Necessary in Korean Patients With Unexplained Developmental Delay/Mental Retardation/Autism Spectrum Disorder

BACKGROUND: All over the world, chromosomal microarray (CMA) is now the first tier diagnostic assay for genetic testing to evaluate developmental delay (DD), mental retardation (MR), and autism spectrum disorder (ASD) with unknown etiology. The average diagnostic yield of the CMA test is known to be about 12.2%, while that of conventional G-banding karyotype is below 3%. This study aimed to assess the usefulness of CMA for the purpose of clinical diagnostic testing in the Korean population. METHODS: We performed CMA and multiplex ligation-dependent probe amplification (MLPA) tests in 96 patients with normal karyotype and unexplained DD, MR, or ASD. The CMA was conducted with CytoScan 750K array (Affymetrix, USA) with an average resolution of 100 kb. RESULTS: Pathogenic copy number variations (CNVs) were detected in 15 patients by CMA and in two patients by MLPA for four known microdeletion syndromes (Prader-Willi/Angelman syndrome, DiGeorge syndrome, Miller-Dieker syndrome and Williams syndrome) designated by National Health Insurance system in Korea. The diagnostic yield was 15.6% and 2.1%, respectively. Thirteen (13.5%) patients (excluding cases with pathogenic CNVs) had variants of uncertain clinical significance. There was one patient with a 17.1-megabase (Mb) region of homozygosity on chromosome 4q. CONCLUSIONS: Our findings suggest the necessity of CMA as a routine diagnostic test for unexplained DD, MR, and ASD in Korea.