• Journal of Genetic Medicine
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• v.8 no.1
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• pp.71-75
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• 2011

A male infant was diagnosed with obstetric brachial plexus injury, congenital muscular torticollis and cleft palate 17 days after birth. His mother presented with gestational diabetes and premature rupture of membranes. Although it is possible that these three disorders arose independently, it is very likely that all three have the same etiologic cause, and we propose that a possible mechanism for this concurrence is related to maternal gestational diabetes. Maternal hyperglycemia mostly affects fetal structures deriving from the neural crest, including the palatine bone, and may have caused the cleft palate observed in this case. Gestational diabetes is also associated with increased frequency of large for gestational age infants and, by extension, with increased risk of birth injuries such as obstetric brachial plexus injury or congenital muscular torticollis associated with large for gestational age infants. Since the children of mothers with gestational diabetes are at increased risk for congenital defects such as cleft palate as well as being large for gestational age, precautions indicated for each respective disorder must be taken during prenatal testing and during birth. However, further studies of more cases are required to evaluate whether the concurrence of obstetric brachial plexus injury, congenital muscular torticollis and cleft palate in this case are complications specifically associated with gestational diabetes or just a simple coincidence.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.194-199
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• 2008

Background: Early identification of pathogens can improve the prognosis of patients with ventilator associated pneumonia (VAP). In the present study, we evaluated the feasibility of performing multiplex PCR for endotracheal aspirates to detect three important pathogens (P. aeruginosa, K. pneumoniae and MRSA) in patients with VAP. Methods: The endotracheal aspirates of 24 patients were collected within 24 hours of the diagnosis of VAP for performing multiplex PCR. Forward and reverse primers were designed to target the specific site of each pathogen (the oprL gene for P. aeruginosa, 16S rRNA for K. pneumoniae and the mec gene for MRSA). We analyzed the clinical data of the VAP patients, including the culture reports for the endotracheal aspirates. Results: Twenty-four patients (M:F=18:6, mean age=$70{\pm}11$) with VAP were enrolled. Pathogens were isolated from 11 patients (P. aeruginosa in 2, K. pneumoniae in 1, MRSA in 2, other enteric Gram negative bacilli in 3, S. pneumoniae in 2 and mixed infection in 1). Multiplex PCR detected three cases of P.aeruginosa (2 cases coincided with the culture reports) and four cases of K. pneumoniae (1 matched with the culture report). PCR detected two MRSA cases, which did not coincide with the culture reports. Conclusion: Multiplex PCR of the endotracheal aspirate showed some ability to detect Gram negative bacilli, although caution is required when interpreting the results.

• Genomics & Informatics
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• v.9 no.2
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• pp.52-58
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• 2011

Osteoporotic fracture (OF), along with bone mineral density (BMD), is an important diagnostic parameter and a clinical predictive risk factor in the assessment of osteoporosis in the elderly population. However, a genome-wide association study (GWAS) on OF has not yet been clarified sufficiently. To identify OF-associated genetic variants and candidate genes, we conducted a GWAS in a population-based cohort (Korean Association Resource [KARE], n=1,427 [case: 288 and control: 1139]) and performed a de novo replication study in hospital-based individuals (Asan and Catholic Medical Center [ACMC], n=1,082 [case: 272 and control: 810]). In a combined meta-analysis, a newly identified genetic locus in an intergenic region at 10p11.2 (near genes FZD8 and ANKRD30A ) showed the most significant association (odd ratio [OR] = 2.00, 95% confidence interval [CI] = 1.47~2.74, p=$1.27{\times}10^{-6}$) in the same direction. We provide the first evidence for a common genetic variant influencing OF and genetic information for further investigation in bone metabolism.

• Journal of Genetic Medicine
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• v.7 no.1
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• pp.59-66
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• 2010

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.

• Journal of Genetic Medicine
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• v.7 no.1
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• pp.53-58
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• 2010

Purpose: To find the most effective method for extraction of cell-free DNA (cf-DNA) from maternal plasma, we compared a blood DNA extraction system (blood kit) and a viral DNA extraction system (viral kit) for non-invasive first-trimester fetal gender determination. Materials and Methods: A prospective cohort study was conducted with maternal plasma collected from 44 women in the first-trimester of pregnancy. The cf-DNA was extracted from maternal plasma using a blood kit and a viral kit. Quantitative fluorescent-polymerase chain reaction (QF-PCR) was used to detect the SRY gene and AMEL gene. The diagnostic accuracy of the QF-PCR results was determined based on comparison with the final delivery records. Results: A total of 44 women were tested, but the final delivery record was only obtained in 36 cases which included 16 male-bearing and 20 female-bearing pregnancies. For the blood kit and viral kit, the diagnostic accuracies for fetal gender determination were 63.9% (23/36) and 97.2% (35/36), respectively. Conclusion: In non-invasive first-trimester fetal gender determination by QF-PCR, using a viral kit for extraction of cf-DNA may result in a higher diagnostic accuracy.

• Journal of Genetic Medicine
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• v.7 no.1
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• pp.82-86
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• 2010

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.

• Journal of Genetic Medicine
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• v.7 no.1
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• pp.67-77
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• 2010

Purpose: The aims of this study are to evaluate psychological impact and quality of life according to the cancer diagnosis and mutation status in Korean families with BRCA mutations. Materials and Methods: Seventeen affected carriers (AC), 16 unaffected carriers (UC) and 13 healthy non carriers (NC) from 13 BRCA mutation families were included in the study. Outcomes were compared with regard to depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory, STAI), optimism (Reevaluation of the Life Orientation test, LOT-R), knowledge of hereditary ovarian cancer, and quality of life (QoL) (SF-36v2 Health Survey, physical component score [PCS], mental component score [MCS]) among three groups. Result: Level of depression, optimism, and PCS were similar in AC, UC, and NC. Anxiety score was elevated in all three groups. MCS was significantly low in AC than in UC and NC (P=0.009, P=0.017). Knowledge of hereditary breast and ovarian cancer was high in AC than NC (P=0.001). MCS was significantly related to whether patient was affected by cancer (P=0.043) and has occupation (P=0.008) or not in multivariable analysis. Conclusion: From this cross sectional study, psychological adverse effect was not related to the carrier status of BRCA mutation. Elevated anxiety in BRCA family members was observed but, independent to affection and the type of genetic mutation. AC showed low mental QoL. Further effort to understand psychological impact and QoL of genetic testing in BRCA family members is required for follow-up in clinical aspects.

• Journal of Genetic Medicine
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• v.8 no.2
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• pp.119-124
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• 2011

Purpose: Supernumerary marker chromosome (SMC) could be associated with various phenotypic abnormalities based on the chromosomal origin of SMCs. The present study aimed to determine the genomic contents of SMCs using chromosomal microarray and to analyze molecular cytogenetic characterizations and clinical phenotypes in patients with SMCs. Materials and Methods: Among patients with SMCs detected in routine chromosomal analysis, SMCs originating from chromosome 15 were excluded from the present study. CGH-based oligonucleotide chromosomal microarray was performed in 4 patients. Results: The chromosomal origins of SMCs were identified in 3 patients. Case 1 had a SMC of 16.1 Mb in 1q21.1-q23.3. Case 2 showed 21 Mb gain in 19p13.11-q13.12. Case 3 had a 4.5 Mb-sized SMC rearranged from 2 regions of 2.5 Mb in 22q11.1-q11.21 and 2.0 Mb in 22q11.22-q11.23. Conclusion: Case 1 presented a wide range of phenotypic abnormalities including the phenotype of 1q21.1 duplication syndrome. In case 2, Asperger-like symptoms are apparently related to 19p12-q13.11, hearing problems and strabismus to 19p13.11 and other features to 19q13.12. Compared with cat-eye syndrome type I and 22q11.2 microduplication syndrome, anal atresia in case 3 is likely related to 22q11.1-q11.21 while other features are related to 22q11.22-q11.23. Analyzing SMCs using high-resolution chromosomal microarray can help identify specific gene contents and to offer proper genetic counseling by determining genotype-phenotype correlations.

• Journal of Genetic Medicine
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• v.8 no.2
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• pp.105-112
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• 2011

Purpose: Sharing genetic information with family members is important for cancer awareness and prevention. The purpose of this study is to examine disclosure patterns of positive BRCA genetic test results to patients' relatives. Materials and Methods: A total of 106 probands who had positive BRCA genetic test results from the Korean Hereditary Breast Cancer Study participated in our study. Subjects were asked whether they had disclosed their genetic test results to first-, second-, and third-degree relatives. Univariate and multivariate analyses were used to identify factors associated with positive result sharing with close and distant relatives. Results: In total, 99 respondents (93.4%) informed at least one at-risk relative of the test result, and they all reported that they had disclosed their genetic test result to a first-degree relative. Communication of test results to other relatives occurred significantly less often, with only 31 of 99 subjects (31.3%) sharing their results with second- or third-degree relatives. In the results of univariate analyses, disclosure of genetic test results to more distant relatives was associated with marital status and months since post-test counseling. The reasons for communication were to provide information about the BRCArelated cancer risk and to recommend the genetic test. Conclusion: Most individuals with the BRCA mutation share their test results with first-degree family members; however, these results reach more distant relatives significantly less often. Therefore, it is necessary to encourage patients' communication with extended family members through systematic genetic counseling.

• Journal of Genetic Medicine
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• v.8 no.2
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• pp.113-118
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• 2011

Purpose: Placental corticotropin-releasing hormone receptor type 1 (CRHR1) expression is reduced in pregnancies with abnormal placental function such as preeclampsia (PE), and the levels and/or function of CRHR1 are genetically influenced. The aim of this study was to investigate the association between the c.33+8199C>T polymorphism in the CRHR1 gene and PE in a Korean population. Materials and Methods: Using a case-control design, the association between the CRHR1 polymorphism and the risk of PE was investigated in 203 individuals with PE and 211 normotensive controls. Genotypes were determined using a SNapShot kit and an ABI Prism 3100 Genetic analyzer. Results: Genotypes and allele frequencies for the CRHR1 polymorphism did not differ between PE and normotensive pregnancies. The variant T allele was more frequent than the ancestral C allele in both of the groups and was more frequent in the controls than in the cases. In risk analysis for PE, there was not an increased risk of preeclampsia in subjects who were concomitant homozygous rare allele genotypes (CC) (OR, 0.3; P=0.15) or heterozygous rare allele genotypes (TC) (OR, 0.8; P=0.29). There were no differences in the complications of PE such as severity or preterm delivery in patients with the CRHR1 polymorphism. Conclusion: Our findings indicate that the CRHR1 polymorphism was not associated with PE in the present Korean study group.