산전 진단에서 관찰된 8번과 22번 염색체 사이의 미세 전좌에 의한 8번 염색체 단완 위성체

오아름(Ah Rum Oh),이봄이(Bom Yee Lee),최은영(Ene Yuong Choi),류현미(Hyun Mee Ryu),이승재(Seung Jae Lee),정지예(Ji Ye Jung),박소연(So Yeon Park) 대한의학유전학회 2011 대한의학유전학회지 Vol.8 No.2

초산인 35세 산모가 고령 임신과 모체혈액선별검사 고위험군을 주소로 양수천자를 실시한 결과 8번 염색체의 단완에 위성체가 붙어 있는 것이 발견되었다. 부모 염색체 검사 결과 모두 정상으로 확인되어 태아에게서 관찰된 8ps현상은 de novo로 판단된다. FISH 검사로 좀 더 자세히 분석한 결과, 8번 염색체와 22번 염색체 사이에 미세한 전좌가 관찰되었다. 태아의 염색체 8번과 22번 사이의 de novo 전좌를 갖고 있었지만 절단 부위가 DNA의 단순 반복 부위이므로 표현형에 영향을 미칠 가능성은 높지 않을 것으로 추측되었고, 임신 기간 동안 초음파상 이상 소견은 관찰되지 않았다. 유전상담을 통해 8번 염색체 단완의 미세 결실 가능성이 설명되었고, 부모의 결정에 따라 추가실험 없이 임신은 유지되었다. 그리고 38주에 정상 표현형의 남아가 분만되었다. 본 증례는 산전 진단에서 세포유전학적 검사로 8번 염색체 단완의 위성체만이 발견되었으나, 추가의 분자세포유전학적 진단으로 8번과 22번 염색체 단완 사이의 미세한 전좌를 확인하였다. 이처럼 보다 정확하고 자세한 분자세포 유전학적 분석들이 산전 진단에서는 필요함을 시사한 사례였다. The authors of the present study report the prenatal detection of a chromosomal abnormality with additional satellites on the distal short arm of chromosome 8. A 35-year-old woman was referred for amniocentesis because of her advanced maternal age and positive result for maternal serum screening test. Cytogenetic analysis of cultured amniocytes showed a satellite 8p chromosome. The satellite 8p chromosome was positive for nucleolus organizer region (NOR) staining. The parents’ karyotypes were normal. Fluorescence in situ hybridization (FISH) study for metaphases of fetal amniocytes revealed a cryptic translocation of chromosomes 8p and 22p. The fetal karyotype was described as 46,XY,8ps.ish t(8;22)(p23.3;p11.2) (D8S504-;D8S504+)dn. The parents decided to continue the pregnancy and a phenotypically normal boy was born at 38 weeks of gestation. In case of de novo terminal NORs detected prenatally, more accurate cytogenetic and molecular analysis should be performed in order to rule out cryptic chromosomal rearrangement among other chromosomes.

Duplication of intrachromosomal insertion segments $4q32{\rightarrow}q35$ confirmed by comparative genomic hybridization and fluorescent $in$ $situ$ hybridization

Kim, Jin-Woo,Park, Ju-Yeon,Oh, Ah-Rum,Choi, Eun-Young,Ryu, Hyun-Mee,Kang, Inn-Soo,Koong, Mi-Kyoung,Park, So-Yeon The Korean Society for Reproductive Medicine 2011 Clinical and Experimental Reproductive Medicine Vol.38 No.4

A 35-year-old man with infertility was referred for chromosomal analysis. In routine cytogenetic analysis, the patient was seen to have additional material of unknown origin on the terminal region of the short arm of chromosome 4. To determine the origin of the unknown material, we carried out high-resolution banding, comparative genomic hybridization (CGH), and FISH. CGH showed a gain of signal on the region of $4q32{\rightarrow}q35$. FISH using whole chromosome painting and subtelomeric region probes for chromosome 4 confirmed the aberrant chromosome as an intrachromosomal insertion duplication of $4q32{\rightarrow}q35$. Duplication often leads to some phenotypic abnormalities; however, our patient showed an almost normal phenotype except for congenital dysfunction in spermatogenesis.

Annual Endovascular Thrombectomy Case Volume and Thrombectomy-capable Hospitals of Korea in Acute Stroke Care

Park Eun Hye,Hwang Seung-sik,Oh Juhwan,Kim Beom Joon,Bae Hee-Joon,Yang Ki Hwa,Choi Ah Rum,Kang Mi Yeon,Subramanian S.V. 대한예방의학회 2023 예방의학회지 Vol.56 No.2

Objectives: Although it is difficult to define the quality of stroke care, acute ischemic stroke (AIS) patients with moderate-to-severe neurological deficits may benefit from thrombectomy-capable hospitals (TCHs) that have a stroke unit, stroke specialists, and a substantial endovascular thrombectomy (EVT) case volume.Methods: From national audit data collected between 2013 and 2016, potential EVT candidates arriving within 24 hours with a baseline National Institutes of Health Stroke Scale score ≥6 were identified. Hospitals were classified as TCHs (≥15 EVT case/y, stroke unit, and stroke specialists), primary stroke hospitals (PSHs) without EVT (PSHs-without-EVT, 0 case/y), and PSHs-with-EVT. Thirty-day and 1-year case-fatality rates (CFRs) were analyzed using random intercept multilevel logistic regression.Results: Out of 35 004 AIS patients, 7954 (22.7%) EVT candidates were included in this study. The average 30-day CFR was 16.3% in PSHs-without-EVT, 14.8% in PSHs-with-EVT, and 11.0% in TCHs. The average 1-year CFR was 37.5% in PSHs-without-EVT, 31.3% in PSHs-with-EVT, and 26.2% in TCHs. In TCHs, a significant reduction was not found in the 30-day CFR (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.76 to 1.12), but was found in the 1-year CFR (OR, 0.84; 95% CI, 0.73 to 0.96).Conclusions: The 1-year CFR was significantly reduced when EVT candidates were treated at TCHs. TCHs are not defined based solely on the number of EVTs, but also based on the presence of a stroke unit and stroke specialists. This supports the need for TCH certification in Korea and suggests that annual EVT case volume could be used to qualify TCHs.

An unusual de novo duplication 10p/deletion 10q syndrome

Bom-Yi Lee,Ju-Yeon Park,Yeon-Woo Lee,Ah-Rum Oh,Shin-Young Lee,Eun-Young Choi,Moon-Young Kim,Hyun-Mee Ryu,So-Yeon Park 대한의학유전학회 2015 대한의학유전학회지 Vol.12 No.1

We herein report an analysis of a female baby with a de novo dup(10p)/del(10q) chromosomal aberration. A prenatal cytogenetic analysis was performed owing to abnormal ultrasound findings including a choroid plexus cyst, prominent cisterna magna, and a slightly medially displaced stomach. The fetal karyotype showed additional material attached to the terminal region of chromosome 10q. Parental karyotypes were both normal. At birth, the baby showed hypotonia, upslanting palpebral fissures, a nodular back mass, respiratory distress, neonatal jaundice and a suspicious polycystic kidney. We ascertained that the karyotype of the baby was 46,XX,der(10)(pter→q26.3::p11.2→pter) by cytogenetic and molecular cytogenetic analyses including high resolution GTG-and RBG-banding, fluorescence in situ hybridization, comparative genomic hybridization, and short tandem repeat marker analyses. While almost all reported cases of 10p duplication originated from one of the parents with a pericentric inversion, our case is extraordinarily rare as the de novo dup(10p)/ del(10q) presumably originated from a rearrangement at the premeiotic stage of the parental germ cell or from parental germline mosaicism.

Prenatal diagnosis of interchromosomal insertion of Y chromosome heterochromatin in a family

Lee, Bom-Yi,Park, Ju-Yeon,Lee, Yeon-Woo,Oh, Ah-Rum,Lee, Shin-Young,Park, So-Yeon,Ryu, Hyun-Mee,Lee, Si-Won Korean Society of Medical Genetics and Genomics 2017 대한의학유전학회지 Vol.14 No.2

Interchromosomal insertion of Y chromosome heterochromatin in an autosome was identified in a fetus and a family. A fetal karyotype was analyzed as 46,XX,dup(7)(?q22q21.1) in a referred amniocentesis at 16 weeks of gestation for advanced maternal age. In the familial karyotype analyses for identification of der(7), the mother, the first daughter and the maternal grandmother showed the same der(7) as the fetus's. CBG-banding was positive at 7q22 region of der(7) that indicated inserted material was originated from heterochromatin. The origin of heterochromatic insertion region in der(7) of the fetus and the mother was found in Yq12 region by fluorescent in situ hybridization with a DYZ1 probe. In the specific analysis of Y chromosomal heterochromatic region of ins(7;Y) of the mother, 15 sequence tagged sites from Yp11.3 region including SRY to Yq11.223 region was not detected. Final karyotypes of the mother, the first daughter and the maternal grandmother were reported as 46,XX,der(7)ins(7;Y)(q21.3;q12q12). All female carriers of ins(7;Y) in the family showed normal phenotype and the mother and the maternal grandmother were fertile. A healthy girl was born at term. We report a rare case of familial interchromosomal insertion of Y chromosome heterochromatin detected only in female family members with normal phenotype that was diagnosed prenatally.

An unusual de novo duplication 10p/deletion 10q syndrome: The first case in Korea

Lee, Bom-Yi,Park, Ju-Yeon,Lee, Yeon-Woo,Oh, Ah-Rum,Lee, Shin-Young,Choi, Eun-Young,Kim, Moon-Young,Ryu, Hyun-Mee,Park, So-Yeon Korean Society of Medical Genetics and Genomics 2015 대한의학유전학회지 Vol.12 No.1

We herein report an analysis of a female baby with a de novo dup(10p)/del(10q) chromosomal aberration. A prenatal cytogenetic analysis was performed owing to abnormal ultrasound findings including a choroid plexus cyst, prominent cisterna magna, and a slightly medially displaced stomach. The fetal karyotype showed additional material attached to the terminal region of chromosome 10q. Parental karyotypes were both normal. At birth, the baby showed hypotonia, upslanting palpebral fissures, a nodular back mass, respiratory distress, neonatal jaundice and a suspicious polycystic kidney. We ascertained that the karyotype of the baby was 46,XX,der(10)($pter{\rightarrow}q26.3::p11.2{\rightarrow}pter$) by cytogenetic and molecular cytogenetic analyses including high resolution GTG-and RBG-banding, fluorescence in situ hybridization, comparative genomic hybridization, and short tandem repeat marker analyses. While almost all reported cases of 10p duplication originated from one of the parents with a pericentric inversion, our case is extraordinarily rare as the de novo dup(10p)/del(10q) presumably originated from a rearrangement at the premeiotic stage of the parental germ cell or from parental germline mosaicism.

Prenatal diagnosis of interchromosomal insertion of Y chromosome heterochromatin in a family

Bom Yi Lee,Ju Yeon Park,Yeon Woo Lee,Ah Rum Oh,Shin Young Lee,So Yeon Park,Hyun Mee Ryu,Si Won Lee 대한의학유전학회 2017 대한의학유전학회지 Vol.14 No.2

Interchromosomal insertion of Y chromosome heterochromatin in an autosome was identified in a fetus and a family. A fetal karyotype was analyzed as 46,XX,dup(7)(?q22q21.1) in a referred amniocentesis at 16 weeks of gestation for advanced maternal age. In the familial karyotype analyses for identification of der(7), the mother, the first daughter and the maternal grandmother showed the same der(7) as the fetus’s. CBG-banding was positive at 7q22 region of der(7) that indicated inserted material was originated from heterochromatin. The origin of heterochromatic insertion region in der(7) of the fetus and the mother was found in Yq12 region by fluorescent in situ hybridization with a DYZ1 probe. In the specific analysis of Y chromosomal heterochromatic region of ins(7;Y) of the mother, 15 sequence tagged sites from Yp11.3 region including SRY to Yq11.223 region was not detected. Final karyotypes of the mother, the first daughter and the maternal grandmother were reported as 46,XX,der(7)ins(7;Y)(q21.3;q12q12). All female carriers of ins(7;Y) in the family showed normal phenotype and the mother and the maternal grandmother were fertile. A healthy girl was born at term. We report a rare case of familial interchromosomal insertion of Y chromosome heterochromatin detected only in female family members with normal phenotype that was diagnosed prenatally.

무정자증 불임남성에서 관찰된 SRY 유전자의 중복을 동반한 일동원체성 derivative Y 염색체

최은영(Eun Young Choi),이봄이(Bom Yi Lee),박주연(Ju Yeon Park),이연우(Yeon Woo Lee),오아름(Ah Rum Oh),이신영(Shin Young Lee),김신영(Shin Young Kim),한유정(You Jung Han),이미범(Mee Bum Lee),류현미(Hyun Mee Ryu),서주태(Ju Tae Seo),박소연( 대한의학유전학회 2010 대한의학유전학회지 Vol.7 No.2

Y 염색체의 구조적 이상은 남성의 정상적인 고환의 분화와 정자생성과정에 영향을 미친다. 본 증례의 무정자증 남성의 혈액세포에서 관찰된 비정상 Y 염색체는 SRY를 포함한 부분적 단완 중복과 Yq12 이질염색질 결실로 재배열된 일동원체성 derivative Y 염색체이다. 이러한 형태의 Y 염색체에 대해서는 매우 드물게 보고되어 있다. 이는 분자세포유전학 및 분자유전학 검사를 통하여 46,X,der(Y)(pter→q11.23::p11.2→pter).ish der(Y)(DYZ3+,DYZ1-,SRY++) 의 결과를 얻었다. 증례의 남성은 비정상 Y 염색체를 가졌음에도 불구하고 정상적인 고환의 크기와 혈액내 성호르몬의 수치는 정상이었다. 하지만 양측성 정계정맥류와 고환생검결과 정자형성기능저하증의 소견을 보였다. 이러한 비정상 Y 염색체는 부계의 감수분열 또는 배발생 초기 단계에서 Y 염색체 자매염색분체의 재배열 또는 Y 염색체내 비대립동종재조합(Non-allelic homologous recombination) 현상 때문에 일어난 것으로 생각되며 환자의 생식세포 분열과정 중 X-Y 성염색체 PAR1 (pseudoautosomal region 1) 부위가 접합하는 2가염색체 (X-Y bivalent) 형성장애기전으로 정자생성 또는 정자성숙 단계에 문제가 생긴 것으로 생각된다. 또한 남성특이영역(male specific region of the Y chromosome, MSY)에서 불임과 관련된 유전자들의 결실과 변이 등의 원인도 배제할 수 없을 것이다. 본 증례는 무정자증 불임남성의 생식과 관련된 표현형이 다양한 원인으로 결정될 수 있음을 시사하며 아울러 불임남성에 대한 보다 정확하고 자세한 분자ㆍ세포 유전학적 분석들이 불임남성의 치료에도 도움이 될 것이라 생각한다. Structural abnormalities of the Y chromosome affect normal testicular differentiation and spermatogenesis. The present case showed a rare monocentric derivative Y chromosome with partial duplication of Yp including the SRY gene and deletion of Yq12 heterochromatin. The karyotype was 46,X,der(Y) (pter→q11.23::p11.2→pter).ish der(Y)(DYZ3+,DYZ1-,SRY++), confirmed through a FISH study. Even though the patient possessed an abnormal Y chromosome, testicular biopsy showed normal testicular volumes in the proband, with gonadal hormonal levels in the normal range but bilateral varicocele and hypospermatogenesis. We speculate that the abnormal Y chromosome arose from sister chromatids during Y chromosome recombination or intra chromosomal NAHR (non-allelic homologous recombination) during meiosis in the patient’s father or in the very early stages of embryogenesis. The derivative Y chromosome might interfere in the meiotic stage of spermatogenesis, leading to the developmental arrest of germ cells. The present case illustrates that the infertility phenotype can have various causes. Also, it emphasizes the importance of accurate and various genetic analyses and could aid in male infertility treatment.

자연 유산에서 드물게 관찰된 Jumping translocation 2례

이연우(Yeon Woo Lee),이봄이(Bom Yi Lee),박주연(Ju Yeon Park),최은영(Eun Young Choi),오아름(Ah Rum Oh),이신영(Shin Young Lee),류현미(Hyun Mee Ryu),강인수(Inn Soo Kang),양광문(Kwang Moon Yang),박소연(So Yeon Park) 대한의학유전학회 2010 대한의학유전학회지 Vol.7 No.1

Jumping translocation (JT)은 여러 세포주에서 하나의 공여 염색체가 둘 이상의 수여 염색체와 염색체 재배열을 보이는 염색체의 구조적 이상으로 종양 세포인 림프성 혈액암에서 빈번하게 관찰되는 획득성(acquired) JT에 비해 체질성(con-stitutional) JT는 매우 드물게 보고되고 있다. 본 증례에서는 자연 유산된 수태산물에서 관찰된 체질성 JT 2례를 보고하고자 한다. 증례 1은 임신 7주 유산아 조직의 세포유전학적 검사에서 핵형분석 결과는 46,XY,add(18)(p11.1)[61]/45,XY,der(18;21)(q10;q10)[32]/46,XY,-18,+mar[16]/46,XY,i(18)(q10)[9]/45,XY,der(15;18)(q10;q10)[6]/46,XY,+1,dic(1;18)(p22;p11.1)[2]/45,XY,der(13;18)(q10;q10)[1]/46,XY[32]로 관찰되었다. 공여 염색체는 18번이고 수여 염색체는 1, 13, 15, 18, 21번이었다. 증례 2는 임신 6주째 자연 유산된 유산아 조직으로부터 세포 유전학적 검사를 실시한 결과, 핵형은 46,XY,der(22)t(9;22)(q12;q13)[22]/46,XY,der(22)t(1;22)(q21;q13)[13]/46,XY,add(22)(q13)[5]/46,XY[23]고 관찰되었다. 공여 염색체는 22번이고 수여 염색체는 1, 9번이었다. 2례 모두 de novo였고 acrocentric 염색체를 수반하였으며 절단점은 대부분 중심절과 중심절 주위, 말단체에 존재하였다. 본 증례는 매우 드물게 관찰되는 체질성 JT로서 임신 초기 세포 분열 단계에서 발생했고 다양한 세포주에서 나타난 비정상 핵형으로 인해 정상적인 배발달이 이루어지지 못하여 자연 유산된 것으로 생각된다. Jumping translocations (JT) are chromosomal rearrangements involving one donor chromosome and several recipient chromosomes. While JTs are frequently observed as acquired chromosomal abnormalities in hematologic malignancies, constitutional JTs are only rarely reported. We report two cases of constitutional JT in chorionic villi derived from the products of conception. The karyotype of the first case was 46,XY,add(18)(p11.1)[61]/45,XY,der(18;21)(q10;q10)[32]/46,XY,-18,+mar[16]/46,XY,i(18)(q10)[9]/45,XY,der(15;18)(q10;q10)[6]/46,XY,+1,dic(1;18)(p22;p11.1)[2]/45,XY,der(13;18)(q10;q10)[1]/46,XY[32]. The donor was a chromosome 18. The recipient chromosomes were chromosomes 1, 13, 15, 18 and 21. In the second case, the karyotype was 46,XY,der(22)t(9;22)(q12;q13)[22]/46,XY,der(22)t(1;22)(q21;q13)[13]/46,XY,add(22)(q13)[5]/46,XY[23]. The donor was a chromosome 22 and recipients were chromosomes 1 and 9. Both cases were de novo. The breakpoints of chromosomes were mostly in centromeric regions, pericentromeric regions, or telomeric regions. Normal cell lines were observed in both cases. This report supports the prior findings that the unstable nature of JT, resulting in chromosomal imbalance, most likely contributed to these early miscarriages.

Paracentric Inversions Found in Prenatal Diagnosis

Lee, Shin Yeong,Lee, Bom Yi,Park, Ju Yeon,Choi, Eun Young,Lee, Yeon Woo,Oh, Ah Rum,Ryu, Hyun Mee,Park, So Yeon Korean Society of Medical Genetics and Genomics 2013 대한의학유전학회지 Vol.10 No.2

Purpose: This study was designed to confirm whether the paracentric inversions of fetuses and parents may be harmless. Materials and methods: We report 10 cases (0.14%) with paracentric inversions among 7,181 prenatal cases observed during prenatal diagnosis performed at Cheil General Hospital between January 2009 and June 2013. We used cytogenetic GTL- and RBG-banding techniques. Results: Of the 10 cases, nine cases were transmitted from each of the parents, and one case was de novo. Nine cases were phenotypically normal up to one month of age after birth. One case was lost to follow-up. We present prenatal diagnosis and follow-up examination of the fetuses with paracentric inversion. Conclusion: Based on our cases, most paracentric inversions are considered to be harmless. The precise identification of paracentric inversions might be clinically important and helpful for genetic counseling.