• Journal of Genetic Medicine
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• 제8권1호
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• pp.53-57
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• 2011

목 적: 윌슨병은 간조직에 구리의 과도한 침착으로 발병하는 상염색체 열성 유전질환이다. 지금까지 ATP7B 유전자가 유일한 원인유전자로 알려져 왔다. 그러나, 약 15%의 환자에서는 ATP7B 유전자 돌연변이가 발견되지 않는다. 본 연구는 ATP7B 유전자의 돌연변이가 발견되지 않은 윌슨병 환자를 대상으로 새로운 원인 유전자를 발견하기 위하여 시행되었다. 대상 및 방법: ATP7B 돌연변이가 발견되지 않은 12명의 윌슨병 환자를 대상으로 ATP7B 와 상호작용을 하는 것으로 알려진 ATOX1, COMMD1, GLRX, DCTN4와 ZBTB16 유전자의 전사부위와 엑손-인트론 경계부위의 염기서열을 분석하였다. 결 과: DCTN4 유전자의 12번 엑손에 존재하는 c.1084A>G(p.Thr362Ala)를 포함하는 3가지의 변이가 환자에서 발견되었다. in silico 분석을 통해 3가지 변이 중 c.1084A>G가 유일하게 단백질 기능 변화를 일으킬 것으로 예측되었다. 176명의 윌슨병 환자와 414명의 정상인을 대상으로 이 변이의 빈도를 조사한 결과, 정상인보다 윌슨병 환자에서 더 높은 빈도를 나타내었다(상대비, odds ratio [OR]=3.14, 95% 신뢰도=1.36-7.22, P=0.0094). 결 론: 본 연구의 결과는 ATP7B 와 상호작용하는 DCTN4 유전자의 c.1084A>G (p.Thr362Ala) 다형성이 윌슨병의 발병과 연관이 있음을 시사한다.

• Journal of Genetic Medicine
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• 제8권1호
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• pp.35-43
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• 2011

목적: 본원에서 최근 10년간 시행한 융모막 융모생검의 적응증에 따른 결과 및 합병증을 조사하고 현재 사용하고 있는 융모막 융모생검의 효용성을 분석해보고자 한다. 대상 및 방법: 2000년 4월부터 2010년 4월까지 최근 10년간 분당차병원 및 강남차병원에서 융모막 융모생검을 시행한 511례의 진료기록 및 검사 결과를 검토하였다. 각각의 환자에 해당되는 모든 적응증을 조사하고 중복을 허용하여 분석하였다. 태아 염색체 검사는 직접법과 배양법을 통하여 시행하였다. 결과: 각각의 적응증을 살펴보면 태아의 비후된 목덜미 두께를 포함한 비정상 초음파 소견이 294례(294/635, 46.3%)로 가장 높았다. 각각의 적응증에 따른 태아 염색체 이상의 양성예측도는 부모 중에 염색체 이상이 있는 경우가 66.7%(14/21)로 가장 높았다. 융모막 융모생검 상 모자이시즘은 3.1% (16/509)였고, 그 중에서 양수검사로 확인된 진모자이시즘은 2례, 태반에 국한된 모자이시즘은 11례였다. 융모막 융모생검 이후 4주 이내에 임신 종결된 경우는 6례로 태아손실률은 1.2% (6/511)였다. 결론: 융모막 융모생검은 산전 유전진단을 하는데 있어서 적합하고 신뢰할 수 있는 시술이다. 융모막 융모생검 결과 모자이시즘을 보이는 경우 반드시 양수검사를 통하여 진모자이시즘인지 태반에 국한된 모자이시즘인지 확인이 필요하다.

• Journal of Genetic Medicine
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• 제17권1호
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• pp.11-15
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• 2020

Purpose: The objective of this study was to analyze the results of several noninvasive prenatal tests (NIPTs) from a single center and confirm their efficacy and reliability. In addition, we aimed to confirm the changes in the number of invasive tests performed after introducing NIPT. Materials and Methods: NIPT data from a large single center from March 2014 to November 2018 were analyzed. Karyotyping was confirmed based on chorionic villus sampling, amniocentesis, or postnatal cord/peripheral blood sampling. Data on maternal age, gestational age, fetal fraction, and ultrasonographic results were analyzed. As the secondary outcome, the number of amniocentesis cases before and after the introduction of NIPT was compared. Results: Overall, 1,591 single pregnancy cases that underwent NIPT were enrolled. The mean maternal age was 36.05 (22-45) years. The average gestational age and fetal fraction were 12⁺¹ (9⁺³ to 27⁺¹) weeks and 10.95% (3.6% to 31.3%), respectively. A total of 1,544 cases (97.0%) were reported to have negative NIPT results and 40 (2.5%) had positive NIPT results. The sensitivity and specificity of the overall abnormalities in NIPT were 96.29% and 99.36%, respectively. The positive predictive value (PPV) and negative predictive value were 72.22% and 99.93% respectively. The mean number of amniocentesis cases were 21.7 per month (21.7±3.9), which significantly decreased from 31.5 per month (31.5±4.8) before conducting NIPT as a screening test. Conclusion: NIPT is currently a useful, powerful, and safe screening test. In particular, trisomy 21 is highly specific due to its high PPV. NIPT can reduce the potential risks of procedure-related miscarriages during invasive testing.

• Journal of Genetic Medicine
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• 제10권1호
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• pp.38-42
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• 2013

Purpose: The purpose of this study was to assess the characteristics of achondroplasia (ACH) diagnosed in fetuses or neonates and to evaluate the usefulness of a molecular genetic testing to confirm ACH. Materials and Methods: The medical and ultrasonographic records of 16 pregnant women, who had molecular genetic testing for ACH performed on their fetus or neonate at the Cheil General Hospital between February 1999 and April 2013, were retrospectively analyzed. Detection of G1138A and G1138C mutations of the fibroblast growth factor receptor 3 (FGFR3) gene was accomplished by polymerase chain reaction - restriction fragment length polymorphism analysis. Results: Of the eight fetuses and two neonates who were suspected of having ACH during pregnancy, four fetuses and one neonate was confirmed to have ACH and they all carried the heterozygous G1138A mutation. Out of 6 cases which had a history of ACH in prior pregnancies, three had genetic information for the previous fetuses while the other three did not. All six fetuses had no mutations at G380R. However, the one fetus of pregnant woman with non-confirmed ACH showed shortened long bone on ultrasound thereafter and the fetus was identified as having oto-spondylo-megaepiphyseal dysplasia after birth. Conclusion: Korean patients with achondroplasia have the heterozygous G1138A mutation that is most commonly defined in other countries. Molecular genetic evaluations of ACH are helpful not only for establishing diagnosis but for appropriate counseling with subsequent pregnancies.

• Journal of Genetic Medicine
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• 제10권1호
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• pp.33-37
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• 2013

Purpose: Myotonic dystrophy 1 (DM1, OMIM 160900) is an autosomal-dominant muscular disorder caused by an expansion of CTG repeats in the 3' UTR of the DMPK gene. Variable expansions of CTG repeats preclude the accurate determination of repeat size. We tried to show the clinical and analytical validity of the application of Southern blotting after long-range PCR was demonstrated in Korean DM1 patients. Materials and Methods: The Southern blotting of long-range PCR was applied to 1,231 cases with clinical suspicion of DM1, between 2000 and 2011. PCR was performed using genomic DNA with forward 5'-CAGTTCACAACCGCTCCGAGC-3' and reverse 5'-CGTGGAGGATGGAACACGGAC-3' primers. Subsequently, the PCR fragments were subjected to gel electrophoresis, capillary transfer to a nylon membrane, hybridization with a labeled (CAG)10 probe. The correlation between clinical manifestations and the CTG repeat expansions were analyzed. Results: Among a total of 1,231 tested cases, 642 individuals were diagnosed with DM1 and the range of the detected expansion was 50 to 2,500 repeats; fourteen cases with mild DM1 ($75{\pm}14$ repeats), 602 cases with classical DM1 ($314{\pm}143$ repeats), and 26 cases with congenital DM1 ($1,219{\pm}402$ repeats). The positive and negative predictive values were 100%. The age at test requested and the CTG repeat numbers were inversely correlated (R=-0.444, P<0.01). Conclusion: This study indicates that Southern blotting after long-range PCR is a reliable diagnostic method DM1.

• Journal of Genetic Medicine
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• 제12권1호
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• pp.38-43
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• 2015

Purpose: Spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders with diverse modes of inheritance. There are several subtypes of SCAs. SCA 8, SCA 12, and SCA 17 are the less common forms of SCAs with limited information available on their epidemiological profiles in Korea. The purpose of this study was to investigate the prevalence of SCA8, SCA12, and SCA17 in Korea. Materials and Methods: Ninety-six unrelated Korean patients were enrolled and showed normal trinucleotide repeats through polymerase-chain reaction (PCR) for the genes ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7, which correspond to SCA1, SCA2, SCA3, SCA6, and SCA7, respectively. PCR products from patients were further analyzed by capillary electrophoresis using fluorescence labeled primers for the genes ATXN8OS, PPP2R2B, and TBP, which correspond to SCA8, SCA12, and SCA17. Results: Three patients had 104, 97, and 75 abnormal expanded repeats in the ATXN8OS gene, the causative gene for SCA8. None of the patients exhibited abnormal repeats in SCA12 and SCA17. Normal trinucleotide repeat ranges of the cohort in this study were estimated to be 17-34 copies (average, $24{\pm}4copies$) for SCA8, 7-18 copies (average, $13{\pm}3copies$) for SCA12, and 26-43 copies (average, $35{\pm}2copies$) for SCA17. Conclusion: This study demonstrated that SCA8, SCA12, and SCA17 are rare in Korean patients with SCA, and further genetic studies are warranted to enhance the mutation detection rate in the Korean SCA population.

• Journal of Genetic Medicine
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• 제13권1호
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• pp.14-19
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• 2016

Purpose: We examined the prevalence and CGG/AGG repeat structure of expanded alleles of the FMR1 gene in preconceptional and pregnant Korean women. Materials and Methods: The CGG repeats in the FMR1 genes of 1,408 women were analyzed by polymerase chain reaction and Southern blot analysis. To estimate the prevalence of expansion alleles, the individuals were divided into low risk and high risk group. Results: Within this population, 98.4% had normal alleles and 1.6% had abnormal alleles including intermediate (0.6%), premutation (0.5%), full mutation (0.1%), and hemizygous (0.4%) alleles. There were 2 premutation alleles (1:666, 95% confidence interval [CI] 1:250-1,776) in the low risk group and 5 premutation alleles (1:15, 95% 1:6-36) in the high risk group. There were 8 intermediate alleles (1:167, 95% CI 1:130-213) in the low risk group and 1 intermediate alleles (1:76, 95% CI 1:11-533) in the high group. Six of the 7 premutation alleles did not contain AGG interruptions within the repeats and 1 had a single AGG interruption. Four of the 9 intermediate alleles contained 2-3 AGG, 4 had a single AGG, and 1 had no AGG interruptions. Conclusion: Our study demonstrates the prevalence and CGG/AGG structure of expansion alleles in Korean women. The identified premutation prevalence is higher than that of other Asian populations and lower than that of Caucasian populations. Although our study is limited by size and population bias, our findings could prove useful for genetic counseling of preconceptional or pregnant women.

• Journal of Genetic Medicine
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• 제8권2호
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• pp.135-138
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• 2011

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. 유전 상담을 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. 이처럼보다 정확하고 자세한 분자세포 유전학적 분석들이 산전 진단에서는 필요함을 시사한 사례였다.

• Journal of Genetic Medicine
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• 제9권1호
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• pp.22-24
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• 2012

Purpose: The aim of this study was to asses the fetal loss rate after mid-trimester amniocentesis. Materials and Methods: This was a retrospective cohort study including singleton pregnant women who underwent mid-trimester amniocentesis at Cheil General Hospital from January 2008 through December 2010. The procedure-related fetal loss was defined as miscarriage within 2 weeks after amniocentesis. We evaluated the fetal loss rate within 2 weeks after amniocentesis and fetal loss rate before 24 gestational weeks. Results: During the study period, a total of 4,356 singleton pregnant women underwent mid-trimester amniocentesis. A total of Five hundred ninety six women were excluded owing to follow up loss and termination of pregnancy due to abnormal karyotype or major anomaly. At our institute, the fetal loss rate within 2 weeks was 0.1% and before 24 gestational weeks was 0.3% after amniocentesis. Conclusion: The fetal loss rate after mid-trimester amniocentesis in our study is lower than previously reported rate. We suggest that amniocentesis is a safe procedure.

• Journal of Genetic Medicine
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• 제9권1호
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• pp.17-21
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• 2012

Purpose: The aim of this study was to analyze parental decisions regarding pregnancies in which the fetus had sex chromosome abnormalities (SCA) over a ten-year period. Materials and Methods: We collected and reviewed records from our hospital for 2001-2010 and a genetic specialist provided-genetic counseling. Results: We diagnosed 130 cases (0.71%) with SCA out of 18,376 prenatal cases from 2001 to 2010. We reviewed the records and the results of all pregnancies. We also included cases (n=84) of apparently normal anatomic fetuses to analyze the factors influencing parental decisions. We excluded 34 cases with an obvious anomaly or a presumably bad outcome and 12 cases that were not followed up. Forty-three couples (51.2%) continued their pregnancies while forty-one (48.8%) terminated them. Of 38 mosaicism cases, 21 (55.3%) were continued. Among the 20 pregnancies assisted by reproductive techniques, 15 (75%) were continued (P=0.02). More pregnancies were continued when genetic counseling was provided (61.9%) compared to cases in which it was not provided (19%) (P=0.01). Conclusion: Genetic counseling is important in providing appropriate information to parents. Establishing guidelines and protocols will help both obstetricians and parents to make informed decisions.