Dried Blood Spot Multiplexed Steroid Profiling Using Liquid Chromatography Tandem Mass Spectrometry in Korean Neonates

최리화,박형두,오현주,이경훈,송정한,이수연 대한진단검사의학회 2019 Annals of Laboratory Medicine Vol.39 No.3

Background: Screening for congenital adrenal hyperplasia (CAH) using immunoassays for 17α-hydroxyprogesterone generates many false-positive results. We developed and validated a liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay for simultaneous quantification of nine steroid hormones in dried blood spot (DBS) samples, and established reference intervals for these hormones. Methods: We examined our method for linearity, precision, accuracy, extraction recovery, and matrix effects and determined the reference intervals of cortisol, 17α-hydroxyproges-terone, 11-deoxycortisol, 21-deoxycortisol, androstenedione, corticosterone, 11-deoxycorticosterone, testosterone, and progesterone in 1,146 DBS samples (from 272 preterm and 874 full-term neonates). Immunoassay and LC-MS/MS methods were compared for 17α-hydroxyprogesterone. Fourteen additional samples were tested to validate the clinical applicability of the LC-MS/MS method. Results: The linearity range was 2.8–828.0 nmol/L for cortisol and 0.9–40.0 nmol/L for the other steroids (R2>0.99). Intra-day and inter-day precision CVs were 2.52–12.26% and 3.53–17.12%, respectively. Accuracy was 80.81–99.94%, and extraction recovery and matrix effects were 88.0–125.4% and 61.7–74.2%, respectively. There was a negative bias, with higher values measured by immunoassay compared with LC-MS/MS (r=0.8104, P< 0.0001). The LC-MS/MS method was successfully applied to the analysis of nine steroids in DBS for screening and diagnosis of CAH using the 14 additional samples. Conclusions: Our method enables highly sensitive and specific assessment of nine steroids from DBS and is a promising tool for clinical analysis of CAH.

The First Korean Case of Childhood Acute Myeloid Leukemia with Inv(11)(p15q22)/NUP98-DDX10 Rearrangement: A Rare but Recurrent Genetic Abnormality

최리화,장미애,유건희,이승태,김희진,김선희 대한진단검사의학회 2014 Annals of Laboratory Medicine Vol.34 No.6

Inv(11)(p15q22)/ NUP98-DDX10 rearrangement is a rare but recurrent chromosomal translocation associated with myeloid malignancies. Structural chromosomal rearrangements of the nucleoporin 98 gene ( NUP98 ) at 11p15.4 produce NUP98 fu- sions with the DDX10 DEAD (Asp-Glu-Ala-Asp) box polypeptide 10 ( DDX10 ) gene on chromosome 11q22 [1]. To date, only 15 such cases, except the present case, with de novo or therapy- related myeloid disorders have been reported [1-8]. Three NUP98-DDX10 fusion isoforms, types I, II, and III, have been reported. The type I fusion, which fuses NUP98 exon 12 (NM_139131.1) with DDX10 exon 6 (NM_004398.2), has been reported in 2 adult therapy-related AML patients [1, 8]. The type II fusion, which fuses NUP98 exon 14 with DDX10 exon 7, has been reported in 12 cases. The type III fusion, which fuses NUP98 exon 15 and DDX10 exon 7, has been reported in 1 adult de novo AML patient with a concurrent case of type II fu- sion [7]. Herein we report a de novo childhood AML patient with inv(11)(p15q22)/ NUP98-DDX10 rearrangement for the first time in Korea.

Evaluation of the Anyplex BRAF V600E Real-Time Detection Assay Using Dual-Priming Oligonucleotide Technology in Fine-Needle Aspirates of Thyroid Nodules

최리화,박경선,김종원,기창석 대한진단검사의학회 2015 Annals of Laboratory Medicine Vol.35 No.6

Background: Several molecular assays have been developed to detect the BRAF V600E mutation in fine needle aspirates (FNAs) for the diagnosis of papillary thyroid cancer. Using a multiplex PCR technique, we evaluated the Anyplex BRAF V600E Real-time Detection (Anyplex) assay and compared its efficacy with that of the Seeplex BRAF V600E ACE Detection (Seeplex) method. Methods: We tested 258 consecutive FNA specimens using the Seeplex and Anyplex assays. Any conflicting results between the two assays were confirmed by using mutant enrichment with 3´-modified oligonucleotide (MEMO) sequencing. The limits of detection (LODs) and reproducibility for each assay were evaluated with serially diluted DNA from a BRAF V600E-positive cell line. Results: The BRAF V600E mutation was detected in 36.4% (94/258) FNA specimens by either the Seeplex or Anyplex assay. Results for the two assays showed 93.4% (241/258) agreement, with a kappa value of 0.861 (95% confidence interval, 0.798-0.923). Of the eight specimens that were BRAF V600E-positive by the Anyplex assay but not by the Seeplex assay, five were found to be BRAF V600E-positive by MEMO sequencing. The mutation detection rate of the Seeplex and Anyplex assays was 79.0% and 84.0%, respectively, in the FNA specimens diagnosed as malignant (n=81). The LOD as determined by probit analysis was 0.046% (95% confidence interval, 0.019-0.532%). Conclusions: The Anyplex assay performed better than the Seeplex assay with respect to the detection of the BRAF V600E mutation.

Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing

최리화,박형두,양미나,기창석,이수연,김종원,송정한,장윤실,박원순 대한진단검사의학회 2017 Annals of Laboratory Medicine Vol.37 No.1

Diagnosis of the urea cycle disorder (USD) carbamoyl-phosphate synthetase 1 (CPS1) deficiency (CPS1D) based on only the measurements of biochemical intermediary metabolites is not sufficient to properly exclude other UCDs with similar symptoms. We report the first Korean CPS1D patient using whole exome sequencing (WES). A four-day-old female neonate presented with respiratory failure due to severe metabolic encephalopathy with hyperammonemia (1,690 μmol/L; reference range, 11.2-48.2 μmol/L). Plasma amino acid analysis revealed markedly elevated levels of alanine (2,923 μmol/L; reference range, 131-710 μmol/L) and glutamine (5,777 μmol/L; reference range, 376-709 μmol/L), whereas that of citrulline was decreased (2 μmol/L; reference range, 10-45 μmol/L). WES revealed compound heterozygous pathogenic variants in the CPS1 gene: one novel nonsense pathogenic variant of c.580C>T (p.Gln194*) and one known pathogenic frameshift pathogenic variant of c.1547delG (p.Gly516Alafs*5), which was previously reported in Japanese patients with CPS1D. We successfully applied WES to molecularly diagnose the first Korean patient with CPS1D in a clinical setting. This result supports the clinical applicability of WES for cost-effective molecular diagnosis of UCDs.

[우리 말 학습과 연구]접미사 《-님》에 대한 사전주석에서 제기되는 몇가지 문제《-님》의 결합적특성과 기능을 론함

최리화 길림성민족사무위원회 1991 중국조선어문 Vol.52 No.-

[학습과 연구]인칭접미사의 의미 - 문법적특성에 대한 고찰

최리화 길림성민족사무위원회 1992 중국조선어문 Vol.61 No.-

A Case of Red Blood Cell Exchange Transfusion in a Patient with Hemoglobin S/b-Thalassemia

최리화,송주선,정헤경,김세미,정철원,박형두,기창석,강은숙,김대원 대한수혈학회 2012 大韓輸血學會誌 Vol.23 No.3

Sickle cell disease and b-thalassemia are caused by abnormal hemoglobin (Hb) derived from mutation of the HBB gene encoding b-globin. Compound heterozygous status for both mutations results in Hb S/b-thalassemia (sickle- b-thalassemia). Vaso-occlusive phenomena and hemolysis are the clinical hallmarks and major causes of mortality. Due to the limited availability of hematopoietic stem cell transplantation with or without gene therapy, red blood cell (RBC) exchange transfusion is the first-line adjunctive therapy. Here we report on a successful reduction of Hb S level in a Tunisian male sickle-b-thalassemia patient by RBC exchange transfusion for primary prophylactic transfusion therapy before flying to his country. Results of both Ion exchange high-performance liquid chromatography and HBB gene mutation analysis indicated sickle-b-thalassemia. Pre-erythrocytapheresis Hb S level was 80.6% of total Hb. Two volumes of RBC exchange were performed using automated erythrocytapheresis with the COBE Spectra Apheresis System (Version 7.0, Caridian BCT, CO, USA). Post-erythrocytapheresis Hb S level was 23.4% of total Hb and hematocrit level was 32.6%, both of which met the target end points. This is the first case report in Korea on successful RBC exchange transfusion in a patient with sickle-b-thalassemia for rapid reduction of pathologic RBCs with Hb S.

Novel SLC37A4 Mutations in Korean Patients With Glycogen Storage Disease Ib

최리화,박형두,고정민,이정호,이동환,홍석진,기창석,이수연,김종원,송정한,YON HO CHOE 대한진단검사의학회 2017 Annals of Laboratory Medicine Vol.37 No.3

Background: Molecular techniques are fundamental for establishing an accurate diagnosis and therapeutic approach of glycogen storage diseases (GSDs). We aimed to evaluate SLC37A4 mutation spectrum in Korean GSD Ib patients. Methods: Nine Korean patients from eight unrelated families with GSD Ib were included. SLC37A4 mutations were detected in all patients with direct sequencing using a PCR method and/or whole-exome sequencing. A comprehensive review of previously reported SLC37A4 mutations was also conducted. Results: Nine different pathogenic SLC37A4 mutations were identified in the nine patients with GSD Ib. Among them, four novel mutations were identified: c.148G>A (pGly50Arg), c.320G>A (p.Trp107*), c.412T>C (p.Trp138Arg), and c.818G>A (p.Gly273Asp). The most common mutation type was missense mutations (66.7%, 6/9), followed by nonsense mutations (22.2%, 2/9) and small deletion mutations (11.1%, 1/9). The most common mutation identified in the Korean population was c.443C>T (p.Ala148Val), which comprised 39.9% (7/18) of all tested alleles. This mutation has not been reported in GSD Ib patients in other ethnic populations. Conclusions: This study expands knowledge of the SLC37A4 mutation spectrum in Korean patients with GSD Ib.

Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations

최리화,정병호,고원중,이수연 대한진단검사의학회 2017 Annals of Laboratory Medicine Vol.37 No.2

Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.

Recent Seroprevalence of Anti-hepatitis A IgG in the Korean Population: a Large, Population-based Study

최리화,박미정,이상곤,이은희 대한진단검사의학회 2020 Laboratory Medicine Online Vol.10 No.3

Background: Because there is limited recent information on this topic, this study investigated the seroprevalence of anti-hepatitis A virus (HAV) immunoglobulin G (IgG) in the South Korean population in 2015–2017. Methods: Anti-HAV IgG seroprevalence data were obtained from the laboratory information system of Green Cross Laboratories, one of the largest referral laboratories in South Korea. Results: During the three-year study period, we obtained test results from 240,840 individuals (124,353 men and 116,487 women) from 1,348 hospitals and local clinics throughout South Korea. The median (range) age of subjects was 38.0 (18.0–97.2) years. The annual seroprevalence of anti-HAV IgG was 53.3%, 53.0%, and 53.1% in 2015, 2016, and 2017, respectively. The median age differed among geographic regions and anti-HAV seroprevalence differed among age groups and geographic regions (P<0.0001). Subjects in their 20’s had a significantly lower rate of anti-HAV IgG-positivity than subjects in their 10’s (odds ratio, [OR] 0.74, 95% CI, 0.69–0.78, P<0.0001), while other age groups had higher rates. Multivariable-adjusted logistic regression analysis showed that women and subjects living in Inchoen, Sejong city, Gangwon province, Gwangju, and North Jeolla province were more likely to be immune to HAV compared to subjects living in Seoul (OR >1.0, P<0.05). Conclusions: This study provides basic information about the recent seroprevalence of anti-HAV IgG in the Korean population and contributes to identifying groups at high risk of an HAV epidemic.