골격 이형성증의 산전 진단에 있어서 초음파 및 분자 유전학적 검사의 유용성에 관한 고찰

김정명 ( Jung Myung Kim ),김나연 ( Na Yeon Kim ),김지윤 ( Ji Yun Kim ),유시연 ( Si Weon You ),오관영 ( Kwna Young Oh ),박원일 ( Won Il Park ),이경아 ( Kyung A Lee ),김영주 ( Young Ju Kim ),전선희 ( Sun Hee Chun ),박미혜 ( Mi Hye P 대한산부인과학회 2010 Obstetrics & Gynecology Science Vol.53 No.6

Objective: To determine the accuracy and usefulness of prenatal ultrasonographic and molecular genetic diagnosis in detection of skeletal dysplasia. Methods: This study was based upon data of the 17 cases of skeletal dysplasia diagnosed by prenatal ultrasound and 7 cases by molecular diagnosis performed among the 17 cases and the 2 cases who has familial skeletal dysplasia by molecular diagnosis during the first trimester at Ewha and Eulji University from March 1998 to August 2005. A final diagnosis was sought on the basis of radiographic studies, molecular testing, or both. Results: The mean gestational age at diagnosis was 24.9 weeks (range, 17 to 35 weeks). Nine cases were diagnosed before 24 weeks. A final diagnosis was obtained in 16 cases (94.1%). There was 1 false-positive diagnosis. The antenatal diagnosis was correct in 14 cases (82.4%). The 8 cases were prenatally confirmed and 1 case was postpartum confirmed using molecular genetic testing and accurate antenatal diagnosis and prediction was done. We were able to rule out skeletal dysplasia through chorionic villus sampling during the first trimester in the 2 cases with the family history with skeletal dysplasia. Conclusion: Prenatal diagnosis of skeletal dysplasia can be a considerable diagnostic challenge. However, skeletal dysplasia is correctly diagnosed on the basis of prenatal meticulous ultrasound and antenatal prediction of lethality was highly accurate. Using prenatal molecular diagnosis, skeletal dysplasia can be diagnosed at first trimester of pregnancy and nonlethal skeletal dysplasia can be confirmed when prenatal ultrasound was nonspecific.

산전 세포유전학적 검사의 임상적 분석: 서울아산병원 4년 간의 경험

심재윤 ( Sim Jae Yun ),김성훈 ( Kim Seong Hun ),김정숙 ( Kim Jeong Sug ),안송미 ( An Song Mi ),서을주 ( Seo Eul Ju ),유한욱 ( Yu Han Ug ),김구환 ( Kim Gu Hwan ),이지영 ( Lee Ji Yeong ),최은영 ( Choe Eun Yeong ),원혜성 ( Won Hye Se 대한산부인과학회 2004 Obstetrics & Gynecology Science Vol.47 No.3

Objective : To review and evaluate a total of 2,372 cases of prenatal cytogenetic diagnoses at Asan Medical Center from 1999 to 2002. Methods : We reviewed to medical records of the patients in whom the procedure for prenatal cytogenetic diagnosis was performed. A total of 1780 cases of amniocentesis, 455 cases of cordocentesis, and 137 cases of chorionic villus sampling were analyzed. The cytogenetic results, indications for prenatal cytogenetic diagnoses, maternal ages, and the profiles of abnormal karyotypes were reviewed. We calculated the positive predictive value of each indication for abnormal fetal karyotypes and evaluated a factor that was the most sensitive marker for abnormal fetal karyotypes. Results : Among the 2,372 cases of prenatal cytogenetic diagnoses, abnormal karyotypes were identified in a total of 158 cases (6.7%). The most frequent indication for prenatal cytogenetic diagnosis was abnormal maternal serum screening (33.9%), followed by ultrasonographic abnomality (22.9%) and old age (20.0%). No significant difference was found between mean maternal age with and without abnormal fetal karyotypes after excluding balanced rearrangements and polymorphisms (31.9±5.3 vs. 32.1±4.5 years). Among the 92 cases of abnormal fetal karyotypes after excluding balanced rearrangements and polymorphisms, the most frequent indication for prenatal cytogenetic diagnosis was ultrasonographic abnormality (58.7%), followed by abnormal maternal serum screening (10.9%). The positive predictive value of ultrasonographic abnormality for abnormal fetal karyotype was 9.9%. Conclusion : Among the several indications for prenatal cytogenetic diagnosis, ultrasonographic abnormality could be the most predictive marker for abnormal fetal karyotypes.

한국인 혈우병 A 가계에 있어 St14 VNTR 부위 DNA Polymorphism 양상 및 이를 이용한 혈우병 A 보인자진단 및 산전진단

김석현(SH Kim),김정구(JK Kim),문신용(SY Moon),이진용(JY Lee),김은주(EJ Kim) 대한산부인과학회 1997 Obstetrics & Gynecology Science Vol.40 No.3

At present, because of enormous variety of mutations in hemophilia A, carrier detection and prenatal diagnosis by DNA analysis has been relied almost always on indirect detection using linkage analysis of DNA polymorphisms withim or near to the factor VIII gene. However, there is marked ethnic variation in the incidence of heterozygosity for a given DNA polymorphism. So it is very important to find out which DNA polymorphism pattern is useful in Korean families with hemophilia A for carrier detection and prenatal diagnosis. To identify the usefulness of DNA polymorphism in St14 VNTR locus for carrier detection and prenatal diagnosis of hemophilia A in Korean populations, we have analysed the DNA polymorphism in St14 VNTR locus in 80 Korean families with hemophilia A using polymerase chain reaction. We could identify 14 alleles in subjects studied, which ranges from 620 bp to 2830 bp. Expected heterozygosity rate, calculated from the allele frequencies, was 78.7%, and observed heterozygosity rate was 71.3% (57/80). Carrier detection was performed in 43 women from families informative with St14 VNTR : Seventeen women were diagnosed as non-carriers, 11 women as carriers. And 15 women were suspected to be carriers since they were from families of sporadic cases of hemophilia A. And prenatal diagnosis was done in 4 pregnant carrier women : noe fetus proved to be normal males, two fetuses to be normal females, and one to be a carrier. And five pregnant women, suspected to be carrier since they were from families of sporadic cases of hemophilia A, underwent prenatal diagnosis : One fetus was diagnosed as a normal mali, one as a normal female, two as possible carriers, and one as a possible affeted mali, whom the analysis of factor VIII level in fetal blood by cordocentesis revealed to be affected by hemophilia A. These data indicate that PCR-based analysis of St14 VNTR is very useful for the carrier detection and prenatal diagnosis of hemophilia A in Korea.

산전진단에 나타나는 공리주의와 우생사상에 대한 인격주의 생명윤리적 고찰

최정임(Choi Jung Im) 가톨릭생명윤리연구소 2015 인격주의 생명윤리 Vol.5 No.1

Medicine and medical practice aims for the good of human being, and the influence of medicine has been more increased owing to the scientific advance in technology and knowledge. As medicine is to choose and apply right scientific methods for a particular symptom or disease to protect human life, the appropriateness of related human behavior is checked not only from a scientific perspective but from a philosophical and anthropological perspective. Prenatal diagnosis is a part of fetal and neonatal medicine, which has been developed to make an accurate diagnosis of the health status of a fetus. It is carried out to provide appropriate support to lower perinatal mortality in the restricted maternal environment. If prenatal diagnosis shows that there is something wrong with a fetus, a proper action should be taken as a follow-up measure, or a treatment plan should be drawn up. Nowadays, however, abortion may be chosen as well as adequate treatment when the fetus is found to have any disease or abnormality. In that case, the result of prenatal diagnosis that was conducted as medical care serves as the ground for abortion that is done as a follow-up measure. What kind of follow-up measure is taken depends on the philosophical and anthropological way of interpreting the result of prenatal diagnosis, not on the scientific result of prenatal diagnosis itself. Accordingly, it is necessary to reconsider the philosophical and anthropological aspect of abortion from the critical standpoint. The logic of justifying abortion as a follow-up measure is the influence of utilitarianism and eugenics. Utilitarianism regards based on that difference sentience as necessary human nature and discriminates human being. It does not approve a right embryo and fetus or a young child's right to life, who belong to human species. According to this theory, it is better choose abortion of the fetus who is diagnosed with any disease or abnormality if the total amount of pleasure and pain that everybody related to the birth of the fetus experience is taken into account. According to eugenics, man is viewed as a higher organism based on the theory of evolution. This theory is affected by the theory of natural selection. According to natural selection, human characteristics are based on genetic character, and the value of a person's existence and future are evaluated by arbitrary or genetic characteristics. If the persons whose genetic quality is excellent, it is chosen. It is possible to reject or remove undesirable genetics traits from the person. According to these two theories, abortion is the oncost likely option to choose as a follow-up measure for prenatal diagnosis. According to personalist bioethics based on personalist tradition, human being is person. Person is a single, independent organic whole. It is an end itself and is an unity compose of soul and body. Person is ultimate being and not substitutable. In personalist bioethics tradition, the fact that a fetus is diagnosed as any disease or abnormality implies that the fetus needs a medical help. This does not change its substantial value and its dignity. Therefore, personalist understanding of human being should serve as the basis of prenatal diagnosis. 의료와 의술은 인간 생명의 선에 봉사하기 위한 목적을 가지며, 오늘날 비약적인 과학기술의 발전과 지식의 확대로 말미암아 그 역할은 더욱 확대되고 있다. 의료는 인간생명에 대하여 적절한 과학기술적 방법을 식별하여 선택ㆍ적용시키는 단계이므로, 이는 과학적 측면 뿐 아니라 철학ㆍ인간학적 측면을 토대로 인간 행위의 적절성을 검토하지 않으면 안 된다. 산전진단은 주산기 영아사망률을 낮추기 위하여 태아가 가지는 모체환경이라는 제약 속에서 태아의 건강상태를 가능한 정확히 가늠하여 적절한 도움을 주기 위하여 발달된 태아의학의 한 부분이다. 따라서 산전진단으로 태아에게 이상이 있다고 진단될 경우, 그 후속행위로 적절한 조치 혹은 치료계획을 수립하는 것이 필요하다. 그러나 오늘날 산전진단으로 태아가 질병이나 장애를 가졌다고 진단되면 그에 따르는 적절한 조치로 치료계획의 수립 외에 낙태가 행해진다. 이 경우 의료로 행해진 산전진단의 검사결과는 후속행위인 낙태에 대한 근거로 작용한다. 산전진단 결과에 따른 후속행위가 달라지는 이유는 산전진단의 결과라는 과학적 측면이 아닌 그 결과를 해석하는 철학적ㆍ인간학적 측면에 있다. 따라서 산전진단에 따른 낙태결정의 경우 그 철학적ㆍ인간학적 측면에 관한 비판적 검토가 필요하다. 산전진단 결과에 따른 낙태 정당화 논리로는 공리주의와 우생사상의 영향이 있다. 공리주의는 이성적 본성을 쾌고감수력으로 보아 인간과 인격체를 구분하고, 인간에 속하는 태아나 유아의 생명권을 인정하지 않는다. 특히 질병이나 이상이 있다고 진단된 태아의 경우, 그들의 탄생으로 인한 관계된 모든 사람의 쾌락과 고통의 총량을 비교하였을 때 낙태를 선택하는 것이 합리적이라 본다. 우생사상에 있어 인간은 진화론에 따른 고등생물로 자연선택에 영향을 받는다. 인간의 특질은 유전적 형질로 환원되어 임의적 유전적 질에 대한 기준에 근거하여 한 인간의 미래와 존재에 대한 가치가 평가된다. 따라서 유전적 질이 우수한 존재의 경우 선택되지만, 평균 질의 저하를 가져오는 존재는 거부와 제거의 대상이 될 수 있다고 본다. 그러므로 공리주의와 우생사상에 따르면 산전진단 결과에 따른 낙태 결정은 가능한 선택이 된다. 인격주의 전통에 근거한 인격주의 생명윤리에 있어 인간은 인격이다. 인격은 영혼과 육체의 유기적이고 체계적인 통합 속에 스스로 존재 원리를 가지는 단일하며 자립적인 완전한 전체이며, 따라서 존재는 실재론적이고 목적론적이며 궁극적이고 대체불가능 한 의미를 가진다. 그러므로 인격주의 생명윤리적 논지에서 질병이나 장애가 있는 태아라는 진단은 도움이 필요한 태아가 처한 특수한 상황이며 그 존재의 본질적 가치와 존엄성에 대한 변화를 의미하지 않는다. 따라서 의술로써 산전진단의 사용이 정당화될 수 있는 근거는 인격주의적 인간이해를 바탕으로 할 때이다.

1970~1990년대 한국 유전자 산전진단기술 도입 — 성 감별에서 기형아 공포로

최은경 한국사회사학회 2022 사회와 역사 Vol.- No.135

This study explores the introduction of genetic prenatal diagnostic technology from the 1970s to the 1990s. It focuses on the ideas and practices of doctors, especially pediatricians and gynecologists, and the opinions of population health experts regarding the technology. It also considers the technology’s social repercussions. With the emergence of cytogenetics in the 1960s, several South Korean doctors attempted amniocentesis for sex determination before childbirth, despite safety problems. From the mid-1970s a few gynecologists who trained in prenatal tests abroad, including Ju Gap-soon and Yang Young-ho, led the adoption of prenatal diagnostic technology in South Korea. Early on the technology was adopted for sex determination, a use that became more popular with the growing availability of ultrasound devices. While promoting the technology for sex determination purposes, doctors also argued that Intellectual Disability, such as Down’s syndrome, could be prevented through prenatal diagnosis. It was important to avoid inheritance of intellectual disabilities from some disabled women in the past; however, after the introduction of prenatal diagnosis, all women at risk of bearing congenital disabilities could get tested. Population health experts worried that sex determination could cause an imbalance in sex ratios; however, they also welcomed prenatal tests to prevent birth defects. Meanwhile, with South Korea’s democratization in the 1990’s, concerns about nuclear power stations and environmental pollution began to be widely shared. This attracted attentions about congenital disabilities. From the 1970s to the 1990s, prenatal diagnosis technology was adopted widely in South Korea due to the demand for sex determination and the efforts of doctors and scientists to inform lay people about the risk of birth defects. Moreover, public fear of congenital disabilities also encouraged their adaptation. 본 연구는 유전자 산전진단기술의 1970년대~1990년대 도입 및 정착 과정을 다룬다. 유전자 산전진단기술 도입을 위한 의학자, 특히 소아과 및 산부인과 의사들의 시도와 담론, 인구보건학자들의 담론을 중심으로 다루되, 그 사회적 반향도 아울러 고찰한다. 1960년대 세포유전학이 새롭게 도입되면서 국내에서도 산전 성 감별의 한 방법으로 양수천자가 시도되었으나 안전성 측면으로 활용되기 어려웠다. 1970년대 중반 주갑순, 양영호 등 해외에서 산전 검사를 수련한 이들을 중심으로 산전진단기술이 본격적으로 실시되기 시작하였다. 초기 산전진단기술은 성 감별 목적으로 널리 활용되었으며 초음파 기기가 다량 보급되면서 산전진단술은 더욱 각광받았다. 의학자들은 성 감별 목적으로 산전진단기술이 활용될 수 있음을 알리는 한편, 다운증후군을 예로 한 지적장애 또한 산전진단술을 통해 미리 출산을 막을 수 있다고 주장하였다. 특히 과거에는 지적장애의 유전성이 관건이었다면, 산전진단술 도입 이후에는 다운증후군을 출산할 수 있는 고위험 정상인 여성의 태아를 미리 검사할 수 있다는 점이 주목받았다. 인구보건학자들은 산전진단기술을 통한 산전 성 감별은 성비 불균형을 초래할 위험이 있다고 보았지만 기형아를 낳을 수 있는 일부 고위험 여성들의 산전 검사는 환영하였다. 1990년대 민주화된 사회를 배경으로 제기된 핵 문제, 환경오염 문제 등도 기형아에 대한 대중적 공포가 자리잡는 데에 기여하였다. 1970년대~1990년대 산전진단기술이 크게 각광받고 보급될 수 있었던 데에는 성 감별 수요, 일반인의 기형아 출산 위험 각인을 위한 의학자들의 노력, 기형아에 대한 공포 등이 작용하였다.

Differences in Surgical Results according to the Prenatal Diagnosis of Critical Congenital Heart Disease

강수경,최광준,송진영 대한주산의학회 2023 Perinatology Vol.34 No.3

Objective: Until recently, the prenatal diagnoses of critical congenital heart disease (CCHD) has increased in Korea and undergone meaningful improvements. We aimed to investigate how the prenatal diagnosis of CCHD is effective in not only survival, but also extra-cardiac morbidity. Methods: We retrospectively reviewed 303 patients who underwent cardiac surgery within 30 days after birth due to CCHD from 2012 to 2020 at the Samsung Medical Center. Of the 303 patients, 157 patients (51.8%) were diagnosed prenatally and whose mortality and morbidity after the operations were compared with 146 patients without prenatal diagnoses. Results: Overall, there was no significant difference between CCHD patients with prenatal diagnoses and postnatal diagnoses in Apgar score, postoperative lengths of hospital stay (30.5 vs. 37.1 days), early postoperative mortality (11.4% vs. 6.2%), and overall mortality (14.6% vs. 11.0%). In addition, neurologic morbidities, hearing impairment, visual impairment, and growth delay did not differ between the groups. The ages of operation were significantly younger and fewer patients were transferred from other hospitals. Conclusion: There were no differences in overall postoperative mortality and morbidity, but younger ages of operation and lower rates of referral were observed due to the prenatal diagnoses.

Validation of QF-PCR for Rapid Prenatal Diagnosis of Common Chromosomal Aneuploidies in Korea

Sung-Hee Han,Jae-Song Ryu,Jeong-Wook An,Ok-Kyoung Park,Hye-Ryoung Yoon,Young-Ho Yang,Kyoung-Ryul Lee 대한의학유전학회 2010 대한의학유전학회지 Vol.7 No.1

목적 : QF-PCR법은 흔한 염색체 이수성에 대한 빠른 산전 진단을 가능하게 하는데, 낮은 가격, 빠른 속도, 그리고 자동화가 가능하여 한꺼번에 많은 검체에 대해 적용할 수 있다는 장점들이 있다. 하지만 아직까지 국내에서 QF-PCR법은 산전 염색체 이수성 선별검사로 주로 사용되는 방법이 아니다. 본 연구에서는 한국인에서 빠른 산전 진단을 목적으로 시행하는 짧은 염기서열 반복(short tandem repeats, STR) 표지자를 이용한 QF-PCR법의 수행능을 검증하고자 한다. 대상 및 방법 : 2007년에서 2009년까지 산전 염색체 이수성 선별을 목적으로 의뢰된 847개의 양수 검체에 대해 QF-PCR법을 시행하였는데 13번, 18번, 21번, X, Y염색체에 위치한 총 20개의 STR 표지자로 구성된 Elucigene kit (Gen-Probe, Abingdon, UK)를 사용하였다. 총 847개의 양수 검체에 대한QF-PCR 결과는 염색체 검사 결과와 비교하였고, STR 표지자의 정보력을 평가하기 위해서 각 표지자에 대해 이형접합체 지수(heterozygosity index)를 구하였다. 결과 : 총 847개 양수 검체에 대한 QF-PCR 검사 결과 19개(2.2%, 19/847)에서 13, 18, 21번 염색체와 X, Y염색체의 수적 이상이 관찰되었는데 염색체 검사에서도 동일한 결과를 보여100% 양성 예측율을 나타냈다. 하지만 염색체 검사 결과 7개(0.8%, 7/847) 검체에서 5개의 균형전좌와 2개의 불균형 염색체 이상이 관찰되었으나 QF-PCR에서는 진단되지 않았다. STR 표지자의 평균 이형접합체 지수(he-terozygosity index)는 0.76으로 서양인에서 보고된 0.8에 비해 다소 낮았다. 본 연구에서 D13S634표지자의 미세수준의 중복(submicroscopic duplication)이 1.4% (12/847)에서 관찰되었는데 이는 한국인에서 특징적인 소견으로 생각된다. 결론 : 본 기관에서는 산전 염색체 이수성 선별을 위한 QF-PCR법을 검증하였으며 효율적이고 신뢰할 수 있는 방법임이 입증되었다. 하지만 QF-PCR결과를 해석하기 위한 지침을 만들기 위해서 검사실마다 독립적으로 각각의 STR표지자에 대한 검증이 필요하며, 또한 QF-PCR법을 통상적인 염색체 검사 업무흐름에 통합하는 것이 필요하다고 사료된다. Purpose: Quantitative fluorescent polymerase chain reaction (QF-PCR) allows for the rapid prenatal diagnosis of common aneuploidies. The main advantages of this assay are its low cost, speed, and automation, allowing for large-scale application. However, despite these advantages, it is not a routine method for prenatal aneuploidy screening in Korea. Our objective in the present study was to validate the performance of QF-PCR using short tandem repeat (STR) markers in a Korean population as a means for rapid prenatal diagnosis. Material and Methods: A QF-PCR assay using an Elucigene kit (Gen-Probe, Abingdon, UK), containing 20 STR markers located on chromosomes 13, 18, 21, X and Y, was performed on 847 amniotic fluid (AF) samples for prenatal aneuploidy screening referred for prenatal aneuploidy screening from 2007 to 2009. The results were then compared to those obtained using conventional cytogenetic analysis. To evaluate the informativity of STR markers, the heterozygosity index of each marker was determined in all the samples. Results: Three autosomes (13, 18, and 21) and X and Y chromosome aneuploidies were detected in 19 cases (2.2%, 19/847) after QF-PCR analysis of the 847 AF samples. Their results are identical to those of conventional cytogenetic analysis, with 100% positive predictive value. However, after cytogenetic analysis, 7 cases (0.8%, 7/847) were found to have 5 balanced and 2 unbalanced chromosomal abnormalities that were not detected by QF-PCR. The STR markers had a slightly low heterozygosity index (average: 0.76) compared to those reported in Caucasians (average: 0.80). Submicroscopic duplication of D13S634 marker, which might be a unique finding in Koreans, was detected in 1.4% (12/847) of the samples in the present study. Conclusion: A QF-PCR assay for prenatal aneuploidy screening was validated in our institution and proved to be efficient and reliable. However, we suggest that each laboratory must perform an independent validation test for each STR marker in order to develop interpretation guidelines of the results and must integrate QF-PCR into the routine cytogenetic laboratory workflow.

세포유전학적 연구를 통한 산전 진단의 염색체 분석

황시목 ( Si Mok Hwang ),권경훈 ( Kyoung Hun Kwon ),오선경 ( Sun Kyung Oh ) 서울대학교 인구의학연구소 2011 人口醫學硏究論集 Vol.24 No.-

Invasive prenatal diagnosis is the most commonly used method for detection of chromosomal aneuploidy or other generic disorders. We performed this study to analyze the indications, distributions of maternal age and cytogenetic results of prenatal cytogenetic examinations, and to evaluate the usefulness of prenatal diagnosis. A cytogenetic analysis of 712 cases (698 amniotic fluid samples, 14 chorionic villi samples) was performed at the GenDix, Inc. from January to December, 2010. The overall rate of chromosomal abnormalities was 7.6% (54 out of 712 cases). The average maternal age of coral subjects was 35.94.2 years, and the most common age group was from 35 to 39 (47.9%). The most frequent indication for prenatal cytogenetic diagnosis was advanced maternal age (>35yr) (42.1%) and positive maternal serum screening (41.0%). Among the 54 cases of chromosomal abnormalities, it contains 28 cases (51.9%) of numerical abnormalities and 26 cases (48.1%) of structural abnormalities. The most frequent structural aberrations were inversion with 69.2% (18 our of 26 cases). Advanced maternal age and positive maternal serum screening must be important screening methods for prenatal diagnosis which is considered to the most effective diagnostic procedure for prenatal cytogenetic studies. Cytogenetic analysis is efficacious method for detection of chromosomal aberration and genetic counseling for parents.

Validation of QF-PCR for Rapid Prenatal Diagnosis of Common Chromosomal Aneuploidies in Korea

Han, Sung-Hee,Ryu, Jae-Song,An, Jeong-Wook,Park, Ok-Kyoung,Yoon, Hye-Ryoung,Yang, Young-Ho,Lee, Kyoung-Ryul Korean Society of Medical Genetics and Genomics 2010 대한의학유전학회지 Vol.7 No.1

목 적: QF-PCR법은 흔한 염색체 이수성에 대한 빠른 산전 진단을 가능하게 하는데, 낮은 가격, 빠른 속도, 그리고 자동화가 가능하여 한꺼번에 많은 검체에 대해 적용할 수 있다는 장점들이 있다. 하지만 아직까지 국내에서 QF-PCR법은 산전 염색체 이수성 선별검사로 주로 사용되는 방법이 아니다. 본 연구에서는 한국인에서 빠른 산전 진단을 목적으로 시행하는 짧은 염기서열 반복(short tandem repeats, STR) 표지자를 이용한 QF-PCR법의 수행능을 검증하고자 한다. 대상 및 방법: 2007년에서 2009년까지 산전 염색체 이수성 선별을 목적으로 의뢰된 847개의 양수 검체에 대해 QF-PCR법을 시행하였는데 13번, 18번, 21번, X, Y염색체에 위치한 총 20개의 STR 표지자로 구성된 Elucigene kit (Gen-Probe, Abingdon, UK)를 사용하였다. 총 847개의 양수 검체에 대한QF-PCR 결과는 염색체 검사 결과와 비교하였고, STR 표지자의 정보력을 평가하기 위해서 각 표지자에 대해 이형접합체 지수(heterozygosity index)를 구하였다. 결 과: 총 847개 양수 검체에 대한 QF-PCR 검사 결과 19개(2.2%, 19/847)에서 13, 18, 21번 염색체와 X, Y염색체의 수적 이상이 관찰되었는데 염색체 검사에서도 동일한 결과를 보여100% 양성 예측율을 나타냈다. 하지만 염색체 검사 결과 7개(0.8%, 7/847) 검체에서 5개의 균형전좌와 2개의 불균형 염색체 이상이 관찰되었으나 QF-PCR에서는 진단되지 않았다. STR 표지자의 평균 이형접합체 지수(he-terozygosity index)는 0.76으로 서양인에서 보고된 0.8에 비해 다소 낮았다. 본 연구에서 D13S634표지자의 미세수준의 중복(submicroscopic duplication)이 1.4% (12/847)에서 관찰되었는데 이는 한국인에서 특징적인 소견으로 생각된다. 결 론: 본 기관에서는 산전 염색체 이수성 선별을 위한 QF-PCR법을 검증하였으며 효율적이고 신뢰할 수 있는 방법임이 입증되었다. 하지만 QF-PCR결과를 해석하기 위한 지침을 만들기 위해서 검사실마다 독립적으로 각각의 STR표지자에 대한 검증이 필요하며, 또한 QF-PCR법을 통상적인 염색체 검사 업무흐름에 통합하는 것이 필요하다고 사료된다. Purpose: Quantitative fluorescent polymerase chain reaction (QF-PCR) allows for the rapid prenatal diagnosis of common aneuploidies. The main advantages of this assay are its low cost, speed, and automation, allowing for large-scale application. However, despite these advantages, it is not a routine method for prenatal aneuploidy screening in Korea. Our objective in the present study was to validate the performance of QF-PCR using short tandem repeat (STR) markers in a Korean population as a means for rapid prenatal diagnosis. Material and Methods: A QF-PCR assay using an Elucigene kit (Gen-Probe, Abingdon, UK), containing 20 STR markers located on chromosomes 13, 18, 21, X and Y, was performed on 847 amniotic fluid (AF) samples for prenatal aneuploidy screening referred for prenatal aneuploidy screening from 2007 to 2009. The results were then compared to those obtained using conventional cytogenetic analysis. To evaluate the informativity of STR markers, the heterozygosity index of each marker was determined in all the samples. Results: Three autosomes (13, 18, and 21) and X and Y chromosome aneuploidies were detected in 19 cases (2.2%, 19/847) after QF-PCR analysis of the 847 AF samples. Their results are identical to those of conventional cytogenetic analysis, with 100% positive predictive value. However, after cytogenetic analysis, 7 cases (0.8%, 7/847) were found to have 5 balanced and 2 unbalanced chromosomal abnormalities that were not detected by QF-PCR. The STR markers had a slightly low heterozygosity index (average: 0.76) compared to those reported in Caucasians (average: 0.80). Submicroscopic duplication of D13S634 marker, which might be a unique finding in Koreans, was detected in 1.4% (12/847) of the samples in the present study. Conclusion: A QF-PCR assay for prenatal aneuploidy screening was validated in our institution and proved to be efficient and reliable. However, we suggest that each laboratory must perform an independent validation test for each STR marker in order to develop interpretation guidelines of the results and must integrate QF-PCR into the routine cytogenetic laboratory workflow.

신생아 중추신경계 이상의 산전 영상 진단의 의의

위지선 ( Ji Sun We ),최세경 ( Sae Kyung Choi ),최정수 ( Jeong Soo Choi ),안현영 ( Hyun Young Ahn ),박인양 ( In Yang Park ),신종철 ( Jong Chul Shin ) 대한주산의학회 2008 Perinatology Vol.19 No.3

목적: 선천성 중추신경계 이상의 산전 진단에서 초음파와 자기공명영상의 소견을 비교하고 자기공명 영상의 장점을 확인하고자 하였다. 방법: 1997년 1월부터 2008년 4월까지의 기간 중에 강남성모병원 산부인과에서 분만한 신생아 중 출생 후 선천성 중추신경계 이상으로 확진 된 신생아들의 의무기록을 후향적으로 분석하여 산전 초음파 및 자기공명영상의 결과를 분만 후의 최종 진단과 비교 분석하였다. 결과: 출생 후 선천성 중추신경계 이상으로 진단된 신생아는 총11명이었고, 산전 자기공명영상이 시행된 경우는 6예이었다. 각각의 적응증은 측뇌실확장증 및 물머리증 3예, 거미막하 낭종 2예, 거대뇌수조증이 1예이었다. 6예 모두에서 부가적인 정보를 얻을 수 있었으며, 이 부가적 정보에 따른 진단은 출생 후의 진단에 더 근접하였다. 결론: 초음파 검사에서 선천성 중추신경계 이상이 관찰되는 태아에서 산전 자기공명영상의 시행은 부가적인 정보를 얻을 수 있고 더 정확한 진단이 가능하며, 보호자 상담과 치료 방침의 결정에 도움이 될 수 있다. Objective: The present study compared the findings of ultrasonography and MRI in the prenatal diagnosis of congenital central nervous system anomalies and identified the merits of MRI. Methods: We retrospectively analyzed the medical records of neonates diagnosed with congenital central nervous system anomaly after birth born at the Department of Obstetrics and Gynecology in Kangnam St. Marys Hospital during the period from January 1997 to April 2008, and compared the findings of prenatal ultrasonography and MRI with the results of postnatal diagnosis. Results: There were a total of 13 neonates postnatally diagnosed with congenital central nervous system anomaly, and 6 of them had prenatal MRI. Among them, ventriculomegaly and hydrocephalus were observed in 3 cases, arachnoid cyst in 2 cases, and megacisterna magna in 1 case. Supplementary information was available for all the 6 cases, and diagnosis based on the supplementary information was closer to postnatal diagnosis. Conclusion: In fetuses in which congenital central nervous system anomaly is observed in ultrasonography, prenatal MRI can provide supplementary information and enable more accurate diagnosis. This can be helpful in counseling the guardians and deciding treatment modality.