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

신새암,유나,정세리,이경아,최종락 대한진단검사의학회 2015 Annals of Laboratory Medicine Vol.35 No.5

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.

췌장암 환자에서 검출된 항-f(ce) 항체 증례보고

나현진,신새암,김신영,이은경,김현옥 대한수혈학회 2016 大韓輸血學會誌 Vol.27 No.2

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). 항-f(ce) 항체는 ce(f) 복합항원에 대한 비예기항체로로서 본 연구에서는 항-f(ce) 항체의 동정을 두 번째로 보고하고자 하였다. 환자는 췌장암진행으로 경피적 간담도 배액술을 받기 위해 입원한 66세 남자로 수혈 전 검사에서 항-f(ce) 항체가 동정되었다. 환자는 수혈력이 있었으며, 항글로불린 단계의 교차시험에서 음성인 혈액으로 수혈 받았고 수혈이상반응은 관찰되지 않았다. 복합항원 ce(f)에 대한 항체의 특이성을 확인하기위한 교차시험상 표현형이 DcE, DCcEe, DCce, DCe인 RhD 양성 혈구에서는 모두 음성을 보인반면, 표현형이 ce, Cce, cE인 RhD음성 혈구에서는 표현형이 ce, cEe인 경우에만 양성을 보였다. 국내에서 단독으로 항-e 항체가 동정됨을 보고한4개의 증례에서 비예기항체 동정 결과를 다시 판독 해본 결과 항-e 항체와 더불어 항-C 항체가 공존하거나 항-Ce 항체를 항-e 항체로 판독했을 가능성을 완전히 배제할 수 없었다. 따라서 Rh 항원에 대한 항체가 동정되는 경우에는 복합항원에대한 항체의 가능성을 항상 염두에 두어야 할 것이다. 또한 국내에서 항-f(ce) 항체를 예민하게 검출하기 위하여 ce(f) 항원 양성 혈구가 표시된 동정용 혈구 세트를 사용하는 것이 추천된다고 하겠다.

Implication and Influence of Multigene Panel Testing with Genetic Counseling in Korean Patients with BRCA1/2 Mutation-Negative Breast Cancer

박지수,신새암,이윤정,이승태,남은지,한정우,이선화,김태일,박형석 대한암학회 2022 Cancer Research and Treatment Vol.54 No.4

Purpose The aim of the study was to evaluate the clinical implication of multigene panel testing of beyond BRCA genes in Korean patients with BRCA1/2 mutation-negative breast cancer. Materials and Methods Between 2016 and 2019, a total of 700 BRCA1/2 mutation-negative breast cancer patients received comprehensive multigene panel testing and genetic counseling. Among them, 347 patients completed a questionnaire about cancer worry, genetic knowledge, and preference for the method of genetic tests during pre- and post-genetic test counseling. The frequency of pathogenic and likely pathogenic variants (PV/LPV) were analyzed. Results At least one PV/LPV of 26 genes was found in 76 out of 700 patients (10.9 %). The rate for PV/LPV was 3.4% for high-risk genes (17 PALB2, 6 TP53, and 1 PTEN). PV/LPVs of clinical actionable genes for breast cancer management, high-risk genes and other moderate-risk genes such as ATM, BARD1, BRIP, CHEK2, NF1, and RAD51D, were observed in 7.4%. Patients who completed the questionnaire showed decreased concerns about the risk of additional cancer development (average score, 4.21 to 3.94; p < 0.001), influence on mood (3.27 to 3.13; p < 0.001), influence on daily functioning (3.03 to 2.94; p=0.006); and increased knowledge about hereditary cancer syndrome (66.9 to 68.8; p=0.025) in post-test genetic counseling. High cancer worry scales (CWSs) were associated with age ≤ 40 years and the identification of PV/LPV. Low CWSs were related to the satisfaction of the counselee. Conclusion Comprehensive multigene panel test with genetic counseling is clinically applicable. It should be based on interpretable genetic information, consideration of potential psychological consequences, and proper preventive strategies. Purpose The aim of the study was to evaluate the clinical implication of multigene panel testing of beyond <i>BRCA</i> genes in Korean patients with <i>BRCA1/2</i> mutation-negative breast cancer.Materials and Methods Between 2016 and 2019, a total of 700 <i>BRCA1/2</i> mutation-negative breast cancer patients received comprehensive multigene panel testing and genetic counseling. Among them, 347 patients completed a questionnaire about cancer worry, genetic knowledge, and preference for the method of genetic tests during pre- and post-genetic test counseling. The frequency of pathogenic and likely pathogenic variants (PV/LPV) were analyzed.Results At least one PV/LPV of 26 genes was found in 76 out of 700 patients (10.9 %). The rate for PV/LPV was 3.4% for high-risk genes (17 <i>PALB2</i>, 6 <i>TP53</i>, and 1 <i>PTEN</i>). PV/LPVs of clinical actionable genes for breast cancer management, high-risk genes and other moderate-risk genes such as <i>ATM, BARD1, BRIP, CHEK2, NF1</i>, and <i>RAD51D</i>, were observed in 7.4%. Patients who completed the questionnaire showed decreased concerns about the risk of additional cancer development (average score, 4.21 to 3.94; p < 0.001), influence on mood (3.27 to 3.13; p < 0.001), influence on daily functioning (3.03 to 2.94; p=0.006); and increased knowledge about hereditary cancer syndrome (66.9 to 68.8; p=0.025) in post-test genetic counseling. High cancer worry scales (CWSs) were associated with age ≤ 40 years and the identification of PV/LPV. Low CWSs were related to the satisfaction of the counselee.Conclusion Comprehensive multigene panel test with genetic counseling is clinically applicable. It should be based on interpretable genetic information, consideration of potential psychological consequences, and proper preventive strategies.

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

조선미,신새암,이경아 대한진단검사의학회 2016 Annals of Laboratory Medicine Vol.36 No.6

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.

Real - Q RV Detection Kit를 이용한 호흡기 감염을 유발하는 바이러스의 동정 성능 평가

이은엽,신새암,김미영,이영경,강희정,김현수,김재석,송원근,김한성 대한진단검사의학회 2019 Laboratory Medicine Online Vol.9 No.1

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. 호흡기바이러스 감염은 세계적으로 가장 흔한 감염성 질환이며 사망을 유발하는 주요 질환 중 하나로 신속하고 정확한 원인바이러스의 검출이 중요하다. 이번 연구에서 실시간 다중 PCR kit 인 Real-Q RV Detection kit(BioSewoom, Korea) 의 호흡기 바이러스 검출한계와 임상적 유용성을 평가하고자 하였다. 총 10 주의 표준 바이러스를 대상으로 하여 Real-Q RV Detection kit 의 검출 한계를 측정하였으며, Allplex Respiratory Panel Assay kit (Seegene, Korea) 와의 비교를 위해 123 개의 비인후 도찰물, 객담 등의 호흡기 검체를 대상으로 하여 제조사의 권고방법대로 검사하였다. 두 kit 간 불일치 결과를 보이는 검체는 염기서열 분석을 시행하였다. 표준바이러스 중 Human rhinovirus (HRV) 의 검출한계가 가장 낮았으며, Parainfuenza virus 2 (PIV 2) 와 Parainfuenza virus 3 (PIV 3)는 상대적으로 높은 검출한계를 보였다. 두 kit 간 일치율은 95.9%에서 100% 까지 나타났다. Real-Q RV Detection kit 에서 Adenovirus (AdV), Allplex Respiratory Panel kit 에서 음성을 보인 검체(3건)는 염기서열분석 결과 모두 AdV 가 확인되었고, Real-Q RV Detection kit 에서 HRV, Allplex Respiratory Panel kit 에서 음성을 보인 검체(1 건)는 염기서열분석 결과 HRV 가 확인되었다. Real-Q RV Detection kit 에서 HRV 로 양성 , Allplex Respiratory Panel kit 에서 Human enterovirus (HEV)가 검출된 검체(1건)는 염기서열분석 결과 HRV 가 확인되었다. Real-Q RV Detection kit 는 호흡기 바이러스의 검출에 있어서 유용할 것이다.

균혈증을 동반한 비피막형 인플루엔자균에 의한 접형동 부비동염 소아 1례

석민정,최규영,신새암,조기영,Seok, Min Jeong,Choi, Kyu Young,Shin, Saeam,Cho, Ky Young 대한소아감염학회 2020 Pediatric Infection and Vaccine Vol.27 No.1

급성 세균성 부비동염은 소아에서 흔하게 발생하는 질환 중 하나로, 바이러스성 상기도 감염 후 5-13%에서 동반하는 것으로 알려져 있다. 접형동에 국한된 부비동염이 발생할 확률은 모든 부비동염의 3% 미만이나 접형동의 구조적 특성상 주위 조직으로 감염이 전파되면 치명적일 수 있다. 비피막형 인플루엔자균(non-typeable Haemophilus influenzae[NTHi])은 급성 세균성 부비동염의 흔한 원인균이나 정상면역인 환아에서 균혈증으로 파급되는 경우는 매우 드물다. 저자들은 특별한 기저질환이 없는 소아가 발열과 두통으로 내원하여 균혈증을 동반한 NTHi에 의한 편측 접형동에 국한된 부비동염이 확인되어 항생제 및 수술적 치료로 호전된 예를 경험하여 보고하는 바이다.

Isochromosome 1q in Childhood Burkitt Lymphoma: The First Reported Case in Korea

임종훈,김효선,신새암,박서진,최종락 대한진단검사의학회 2015 Annals of Laboratory Medicine Vol.35 No.6

Secondary Germline CDKN2A Mutation Identified using Liquid Biopsy in a Patient with Esophageal Cancer

장한밀,원동주,신새암,박성용,김대준,이승태,최종락 대한진단검사의학회 2022 Laboratory Medicine Online Vol.12 No.1

Liquid biopsy is a non-invasive method for tumor genotyping through detecting the circulating tumor DNA (ctDNA). Here, we describe the case of an esophageal squamous cell cancer patient in which a germline CDKN2A mutation was identified incidentally through liquid biopsy. The preoperative sample analysis revealed a total of five alterations in CDKN2A, TP53, FAT1, and KMT2C genes using next-generation sequencing data. The CDKN2A p.R87W was confirmed as a germline mutation, which is likely a pathogenic variant revealed through peripheral leukocyte DNA analysis. The patient underwent esophagectomy and sequential adjuvant chemoradiation therapy. After the surgery, the variant allele frequencies of somatic variants tended to decrease throughout the treatment. In addition to the detection of somatic variants, ctDNA testing can also provide information on the germline cancer susceptibility variants.

A Case of Chronic Myeloid Leukemia with Micro BCR::ABL1 Rearrangement: Precaution in Reverse Transcription PCR to Prevent False Negativity

김서완,김홍경,신새암,정해림 대한진단검사의학회 2023 Laboratory Medicine Online Vol.13 No.4

We report a patient negative for BCR::ABL1 in qualitative reverse transcription (RT)-PCR but subsequently reported to be positive for t(9;22)(q34;q11.2) in conventional karyotyping. The patient was finally diagnosed with micro-type chronic myeloid leukemia after re-examining RT-PCR and performing targeted RNA sequencing. Through this case, we highlight the risk of false negativity when interpreting RT-PCR to detect micro-type fusion. Upon re-examining RT-PCR results, the patient’s internal control band was thicker than others. After extending the electrophoresis run time, a 911-bp internal control band and a target band around the level of 1.0 kb were separated. We confirmed a fusion breakpoint (BCR exon 19 and ABL1 exon 2) by targeted RNA sequencing, and it corresponds to 1,012 bp-sized e19a2 (c3a2) type among four micro-type fusion transcripts that RT-PCR HemaVision® kit M6B can detect.

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

김지은,유철주,신새암,이승태,최종락 대한진단검사의학회 2016 Annals of Laboratory Medicine Vol.36 No.5

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.