염색체 Microarray 검사의 임상적 적용

서을주(Eul-Ju Seo) 대한의학유전학회 2010 대한의학유전학회지 Vol.7 No.2

염색체 microarray 검사는 유전체 전체를 한번에 검색하여 초현미경적인 염색체 이상을 매우 정밀하고 정확하게 검출할 수 있다. 외국에서는 현재 자주 활용되는 임상 진단 검사로 자리잡았고, 염색체 검사 또는 표적 부위를 검출하는 FISH 검사나 PCR 기반의 분자유전학적 방법을 대체하고 있다. 최근 발표된 consensus 들은 염색체 microarray 검사를 비특이적인 다발성 기형, 발달지연 또는 정신지체, 자폐증상질환의 환자에서는 염색체 검사보다 먼저 시행할 수 있는 검사로 제안하였다. 염색체 microarray 검사는 핵형 분석에서 검출된 염색체 불균형을 검증하기 위해 염색체 검사에 보조적으로 활용할 수 있고, 염색체 이상에 대한 보다 정확하고 종합적인 분석이 가능하다. 그러나 염색체 microarray 검사는 균형재배열의 염색체 이상과 low-level 모자이시즘을 검출하기 어렵고, 임상적 중요성이 불명확한 CNV에 대한 해석과 검사비용이 고가라는 한계점이 있다. 이러한 이유로 인해 현재로서는 염색체 microarray 검사가 산전 진단 목적으로는 고식적인 염색체 검사를 대신할 수는 없다는 의견이다. 임상검사실에서 염색체 microarray 검사 시행 시, 유전학적 및 세포유전학적 지식과 경험이 결과 분석과 해석 과정에서 요구되며, 적절한 검증 과정 단계와 유전상담이 동반되어야 한다. Chromosomal microarray analysis (CMA) enables the genome-wide detection of submicroscopic chromosomal imbalances with greater precision and accuracy. In most other countries, CMA is now a commonly used clinical diagnostic test, replacing conventional cytogenetics or targeted detection such as FISH or PCR-based methods. Recently, some consensus statements have proposed utilization of CMA as a first-line test in patients with multiple congenital anomalies not specific to a welldelineated genetic syndrome, developmental delay/intellectual disability, or autism spectrum disorders. CMA can be used as an adjunct to conventional cytogenetics to identify chromosomal abnormalities observed in G-banding analysis in constitutional or acquired cases, leading to a more accurate and comprehensive assessment of chromosomal aberrations. Although CMA has distinct advantages, there are several limitations, including its inability to detect balanced chromosomal rearrangements and low-level mosaicism, its interpretation of copy number variants of uncertain clinical significance, and significantly higher costs. For these reasons, CMA is not currently a replacement for conventional cytogenetics in prenatal diagnosis. In clinical applications of CMA, knowledge and experience based on genetics and cytogenetics are required for data analysis and interpretation, and appropriate follow-up with genetic counseling is recommended.

성인 급성림프아구성백혈병에서 Philadelphia 염색체와 BCR-ABL 재배열의 분석

서을주,박찬정,지현숙,이규형,서철원,김우건 대한임상병리학회 1999 대한임상병리학회지 Vol.19 No.3

Turner syndrome presented with tall stature due to overdosage of the <i>SHOX</i> gene

Seo, Go Hun,Kang, Eungu,Cho, Ja Hyang,Lee, Beom Hee,Choi, Jin-Ho,Kim, Gu-Hwan,Seo, Eul-Ju,Yoo, Han-Wook The Korean Society of Pediatric Endocrinology 2015 Apem Vol.20 No.2

<P>Turner syndrome is one of the most common chromosomal disorders. It is caused by numerical or structural abnormalities of the X chromosome and results in short stature and gonadal dysgenesis. The short stature arises from haploinsufficiency of the <I>SHOX</I> gene, whereas overdosage contributes to tall stature. This report describes the first Korean case of Turner syndrome with tall stature caused by <I>SHOX</I> overdosage. The patient presented with primary amenorrhea and hypergonadotropic hypogonadism at the age of 17 years. Estrogen replacement therapy was initiated at that time. She displayed tall stature from childhood, with normal growth velocity, and reached a final height of 190 cm (standard deviation score, 4.3) at the age of 30 years. Her karyotype was 46,X, psu idic(X)(q21.2), representing partial monosomy of Xq and partial trisomy of Xp. Analysis by multiplex ligation-dependent probe amplification detected a duplication at Xp22.3-Xp22.2, encompassing the <I>PPP2R3</I> gene near the 5'-end of the <I>SHOX</I> gene through the <I>FANCD</I> gene at Xp22.2.</P>

중환자실에서 분리된 methicillin내성 포도상구균의 분자 역학적 조사

서을주,배직현 대한임상병리학회 1996 대한임상병리학회지 Vol.16 No.4

The phenotypic heterogeneity of patients with Marfan-related disorders and their variant spectrums

Seo, Go Hun,Kim, Yoon-Myung,Kang, Eungu,Kim, Gu-Hwan,Seo, Eul-Ju,Lee, Beom Hee,Choi, Jin-Ho,Yoo, Han-Wook Williams & Wilkins Co 2018 Medicine Vol.97 No.20

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>Marfan syndrome (MFS) and Loeys–Dietz syndrome (LDS) are the connective tissue disorders characterized by aortic root aneurysm and/or dissection and various additional features. We evaluated the correlation of these mutations with the phenotypes and determined the clinical applicability of the revised Ghent criteria.</P><P>The mutation spectrum and phenotypic heterogeneities of the 83 and 5 Korean patients with suspected MFS and LDS were investigated as a retrospective manner. In patients with suspected MFS patients, genetic testing was conducted in half of 44 patients who met the revised Ghent criteria clinically and half of 39 patients who did not meet these criteria.</P><P>Fibrillin1 gene (<I>FBN1</I>) variants were detected in all the 22 patients (100%) who met the revised Ghent criteria and in 14 patients (77.8%) who did not meet the revised Ghent criteria (<I>P</I> <I>=</I> .0205). Patients with mutations in exons 24–32 were diagnosed at a younger age than those with mutations in other exons. Ectopia lentis was more common in patients with missense mutations than in patients with other mutations. Aortic diameter was greater in patients with missense mutations in cysteine residues than in patients with missense mutations in noncysteine residues. Five LDS patients had either <I>TGFBR1</I> or <I>TGFBR2</I> variants, of which 1 patient identified <I>TGFBR1</I> variant uncertain significance.</P><P>The revised Ghent criteria had very high clinical applicability for detecting <I>FBN1</I> variants in patients with MFS and might help in selecting patients with suspected MFS for genetic testing.</P></▼2>

영유아의 동종 조혈모세포이식에서 주사용 Busulfan과 Cyclophosphamide 전처치의 유용성

서종진,김윤정,이미정,최은석,문형남,김태형,서을주,박찬정,지현숙 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.2

연구배경: HSCT의 중요한 전처치 약제 중 하나인 경구 Bu은 위장관 흡수가 일정하지 않고 환자에 따라 약리에 크게 차이가 나는 경우가 있으며, 영유아에서는 경구 복용이 어렵고 구토하는 경우도 많아 일정한 혈장 농도를 얻기가 힘들어 간독성 및 전처치 효과가 문제가 될 수 있다. 이러한 경구 Bu의 여러가지 단점들을 극복하기 위해 그 수용성을 개선하여 최근 IV Bu이 개발되었다. 본 연구에서는 경구 약제 복용이 난이한 영유아에게 IV Bu를 사용한 전처치법을 시행한 단일기관의 HSCT 경험을 보고하고자 하였다. 방법: 울산의대 서울아산병원 소아과에서 2000년 7월부터 2002년 4월까지 IV Bu을 포함한 전처치로 HSCT를 시행한 4세 미만의 영유아 총 6예를 대상으로 후향적인 의무기록분석을 시행하였다. IV Bu는 0.8 mg/kg/dose로 6시간마다 4일간 총 16 dose를 투여하였고(D-7~D-4), 이어 Cy 60 mg/kg/dose를 24시간마다 2일간 투여하였다(D-3, D-2). 결과: 대상 질환은 급성 백혈병이 5예, CGD가 1예이었으며 HSCT 시 대상 연령의 중앙값은 2년 2개월이었다. 3예는 조직적합성일치 혈연간 HSCT이었으며, 나머지 3예는 조직적합성일치 비혈연간 HSCT이었다. 환자에 주입된 CD34+ 세포는 15.3×10^(6) (5.0~31.7×10^(6))/kg이었다. 점막염 grade 4를 보인 1예를 제외하고는 모두 경미한 점막증상을 보였으며, 간독성은 grade 1~3정도였고, 중추신경계 독성을 보인 증례는 없었으며, VOD는 경증 1예만 관찰되었다. 호중구 생착의 중앙값은 D+13일, 혈소판은 D+23일이었으며 중증으로 사망한 1예를 제외하고는 aGVHD는 없었다. 생존 환자 4명 중 백혈병 환자 3명은 추적관찰기간 각기 18, 28, 28개월로 현재 모두 완전관해 상태이며, CGD 환자 1명은 NBT 검사결과 정상화되었고 HSCT 후 이전에 반복되던 감염증이 발생되지 않았다. 결론: IV Bu는 영유아에서 HSCT 시 사용의 편이성, 높은 순응도, 부작용 감소의 가능성 및 신뢰할 수 있는 전처치 효과 등의 유용성이 있어 경구 Bu의 대체 약제로 추천된다. Background: Oral busulfan (Bu) and cyclophosphamide (Cy) is a well established pretransplant conditioning regimen, but the use of oral Bu is limited by the difficulty of oral administration in young children and by the liver toxicity following unpredictable intestinal drug absorption. Several studies on intravenous (IV) Bu (Busulfex®) showed more consistent pharmacokinetic parameters than those seen with oral Bu in children. This study was carried out to ascertain the utility of IV Bu and Cy conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in young children with acute leukemia. Methods: Six patients less than 4 years of age who underwent allogeneic HSCT using IV BuCy conditioning regimen at Asan Medical Center from July 2000 to April 2002 were analyzed retrospectively with regard to the tolerability and toxicity of IV Bu and the transplant data. IV Bu was given 16 doses of 0.8 mg/kg every 6 hr, and 2 doses of 60 mg/kg Cy were daily. All the patients received short-term methotrexate and cyclosporin A as GVHD prophylaxis, and G-CSF starting at day +5. Results: The diagnosis of 6 patients were AML(3), ALL(1), acute mixed lineage leukemia(1) and chronic granulomatous disease(1). The median age at HSCT was 2 years and 2 months, and all the 5 patients with leukemia were in complete remission at the time of transplant. Three received HSC from matched sibling donor and the other 3 from unrelated donors. The mean CD34+ cell dose/kg of recipient body weight was 15.3×10^(6) (5.0~31.7×10^(6)). Median day of engraftment to >500 neutrophil/μL was day +13 (11~16), and >20,000 platelet/μL was day +23(12~30). Early transplant-related toxicities were acceptable; grade 1 mucositis (except 1 case with grade 4) and grade 1~3 hepatotoxicities in all. One case developed mild hepatic veno-occlusive disease, and there were no case with CNS toxicity. The chimerism status documented by short tandem repeats-PCR revealed complete chimerism in 5 cases and mixed chimerism in 1. There were 2 transplant-related mortalities, one due to severe acute GVHD and the other due to secondary graft failure. Conclusion: IV Bu was well tolerated, and could avoid the difficulties of oral ingestion in younger children, with moderate toxicity. It should be considered as replacement for oral busulfan in conditioning regimen of HSCT in infant and young children.

Identification of 1p36 deletion syndrome in patients with facial dysmorphism and developmental delay

Seo, Go Hun,Kim, Ja Hye,Cho, Ja Hyang,Kim, Gu-Hwan,Seo, Eul-Ju,Lee, Beom Hee,Choi, Jin-Ho,Yoo, Han-Wook The Korean Pediatric Society 2016 Clinical and Experimental Pediatrics (CEP) Vol.59 No.1

Purpose: The 1p36 deletion syndrome is a microdeletion syndrome characterized by developmental delays/intellectual disability, craniofacial dysmorphism, and other congenital anomalies. To date, many cases of this syndrome have been reported worldwide. However, cases with this syndrome have not been reported in Korean populations anywhere. This study was performed to report the clinical and molecular characteristics of five Korean patients with the 1p36 deletion syndrome. Methods: The clinical characteristics of the 5 patients were reviewed. Karyotyping and multiplex ligation-dependent probe amplification (MLPA) analyses were performed for genetic diagnoses. Results: All 5 patients had typical dysmorphic features including frontal bossing, flat right parietal bone, low-set ears, straight eyebrows, down-slanting palpebral fissure, hypotelorism, flat nasal roots, midface hypoplasia, pointed chins, small lips, and variable degrees of developmental delay. Each patient had multiple and variable anomalies such as a congenital heart defect including ventricular septal defect, atrial septal defect, and patent duct arteriosus, ventriculomegaly, cryptorchism, or hearing loss. Karyotyping revealed the 1p36 deletion in only 1 patient, although it was confirmed in all 5 patients by MLPA analyses. Conclusion: All the patients had the typical features of 1p36 deletion. These hallmarks can be used to identify other patients with this condition in their early years in order to provide more appropriate care.

Vitek Enteric Pathogen Screen Card법에 의한 장내병원균 선별검사

서을주,배직현 대한임상병리학회 1992 대한임상병리학회지 Vol.12 No.2

Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome with deletion of chromosome 11p14.3p12

Seo, Go Hun,Kim, Yoon-Myung,Kim, Gu-Hwan,Seo, Eul-Ju,Choi, Jin Ho,Lee, Beom Hee,Yoo, Han-Wook Korean Society of Medical Genetics and Genomics 2018 대한의학유전학회지 Vol.15 No.1

WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome is a rare contiguous gene deletion syndrome caused by deleting genes including WT1 and PAX6 genes in 11p13 region, which is characterized by Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability. We report the clinical and cytogenetic characteristics of one Korean patient with WAGR syndrome. The patient shows bilateral sporadic aniridia and genital anomalies at 2 months of age. A heterozygous 14.5 Mb interstitial deletion of 11p14.3p12 region was detected by array comparative genomic hybridization. At 2 years and 10 months of age, Wilms tumor is found through regularly abdominal ultrasonography and treated by chemotherapy, radiation therapy and surgery.

소아기 급성 림프구성 백혈병에서 E2A-PBX1 검색에 의한 미세잔존 백혈병의 의의 및 지연강화요법의 효과

서종진,김은정,박준은,서을주,박찬정,지현숙,문형남,김태형 大韓血液學會 2001 大韓血液學會誌 Vol.36 No.1