Various automated chemiluminescence immunoassay (CLIA) analyzers for the detection of antibodies ... more Various automated chemiluminescence immunoassay (CLIA) analyzers for the detection of antibodies to hepatitis C virus (HCV) are now commercially available in clinical laboratories and are replacing conventional enzyme immunoassays. We investigated the performance of four anti-HCV CLIAs (the Architect Anti-HCV assay on the Architect i2000 system, the Vitros Anti-HCV assay on the Vitros ECiQ Immunodiagnostic System, the Access HCV Ab PLUS assay on the UniCel DxI 800 analyzer, and the newly developed Elecsys Anti-HCV assay on the Cobas e 411 analyzer). The total percent coefficient of variation values of imprecision were 3.5 to 5.7% with positive control materials and 7.2 to 10.2% with negative control materials. The agreement between the results of the Elecsys, Architect, Vitros, and Access CLIAs ranged from 94.5 to 98.1%. The clinical sensitivity of all CLIAs was 100%. Each CLIA showed excellent reproducibility and clinical sensitivity. The Elecsys, Architect, Vitros, and Access CLIAs showed clinical specificities of 98.2, 98.8, 96.5, and 98.2%.
Determination of the copy number of the survival motor neuron (SMN) gene is important for detecti... more Determination of the copy number of the survival motor neuron (SMN) gene is important for detecting spinal muscular atrophy (SMA) carriers and compound heterozygous patients. Multiplex ligationdependent probe amplification (MLPA) assay is a simple and efficient technique used for detecting variations in the copy numbers of different genes. Race- and ethnicity-based variation in the SMA carrier frequency and the '2+0' genotype of SMN1 are important factors that should be considered when estimating the risk of being an SMA carrier. Since SMN2 plays a disease-modifying role, accurate determination of SMN2 copy numbers in SMA patients can serve as a useful prognostic tool. Therefore, information on the SMN2 genotype distributions in normal populations will be helpful in selecting appropriate reference samples for MLPA analysis. To determine SMA carrier frequencies and SMN genotype distribution, we determined the copy numbers of SMN1 and SMN2 genes using the MLPA assay in 100 unrelated Korean individuals with no family history of SMA. The frequency of SMA carriers in the Korean population appears to be 1 in 50, which indicates that the prevalence of SMA among Koreans is the same as that among individuals in the Western countries. Two of the 100 normal individuals enrolled in this study showed 3 copies of the SMN1 gene. Therefore, 1.0% of the 198 normal alleles in this population was estimated to be 2-copy alleles ('2+0' genotype). SMN2 copy numbers showed a high degree of individual variation. Our results showed that 64% of the individuals had 2 copies of SMN2, but 36% individuals had between 0, 1, or 3 copies of the gene.
Hereditary nonpolyposis colorectal cancer (HNPCC) (MIM #114500), also called Lynch syndrome, is a... more Hereditary nonpolyposis colorectal cancer (HNPCC) (MIM #114500), also called Lynch syndrome, is an autosomal dominantly inherited cancer syndrome accounting for 1-5% of all colorectal cancer cases. In a study of three Korean families with HNPCC consistent with the revised Bethesda criteria, DNA testing revealed three novel HNPCC germline mutations in two genes: namely, MLH1, with an insertion resulting in a frameshift and a premature stop codon; MSH2, with a deletion at nucleotide 633, exon 3, which results in stop of translation at codon 213; and MSH2, with a deletion at nucleotide 1413, exon 9, resulting in a frameshift and a premature stop codon. In the first two families, there were splice mutations at c.2006-6 thymine to cytosine. The clinical implications of a frameshift mutation are discussed, along with the significance of common underlying splice mutations existing within families with HNPCC.
A rare karyotypic event, der(1;15)(q10;q10), which involves the whole long arms of chromosomes 1 ... more A rare karyotypic event, der(1;15)(q10;q10), which involves the whole long arms of chromosomes 1 and 15, has been reported in patients with various conditions, including acute myelogenous leukemia, myelodysplastic syndrome, polycythemia vera, and multiple myeloma. Only 27 cases of unbalanced der(1;15)(q10;q10) have been documented in the literature as single or complexed chromosomal abnormalities in hematological malignancies. Here, we describe two cases of acute lymphoblastic leukemia with der(1;15)(q10;q10), and review the previous reports. Although more case studies are needed, we suggest that der(1;15)(q10;q10) should be considered a nonrandom chromosomal abnormality in hematological malignancies including both lymphoid and myeloid neoplasms.
We report the case of a 38-year-old man with acute promyelocytic leukemia (APL) showing a distinc... more We report the case of a 38-year-old man with acute promyelocytic leukemia (APL) showing a distinct breakpoint cluster region 2 (bcr2) variant transcript. Findings from bone marrow, cytogenetic, fluorescence in situ hybridization, and qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were consistent with the diagnosis of APL. Although PCR products of size 841 bp and 984 bp were amplified from bone marrow specimen, the quantitative PCR (RQ-PCR) findings were negative. Given the discrepancy in PCR results, sequencing of PCR products was performed to determine the detailed composition of these fusion transcripts. By cloning and sequencing, we discovered that these two bands were isoforms, in which one exon (exon 5, 144 bp) of the PML gene was spliced out of the smaller products (minor PCR products); one sequence (G) insertion and one base substitution (T-->C) of PML exon 4 generate a stop codon in the smaller fusion transcript. In addition, a search of the Ensembl database revealed that these variant PML/RARA fusion transcripts were composed of exon 7a insertion of the PML gene and partial deletion (46 bp) of exon 3 of the RARA gene, in addition to inserted sequences of intron 7 of PML and genomic sequence ATCT of unknown origin at the fusion junction site. Although the biological significance of most atypical transcripts remains unclear, sequence analysis of these atypical products should be performed, to reveal the composition of such a fusion transcript and elucidate the molecular mechanism.
Various automated chemiluminescence immunoassay (CLIA) analyzers for the detection of antibodies ... more Various automated chemiluminescence immunoassay (CLIA) analyzers for the detection of antibodies to hepatitis C virus (HCV) are now commercially available in clinical laboratories and are replacing conventional enzyme immunoassays. We investigated the performance of four anti-HCV CLIAs (the Architect Anti-HCV assay on the Architect i2000 system, the Vitros Anti-HCV assay on the Vitros ECiQ Immunodiagnostic System, the Access HCV Ab PLUS assay on the UniCel DxI 800 analyzer, and the newly developed Elecsys Anti-HCV assay on the Cobas e 411 analyzer). The total percent coefficient of variation values of imprecision were 3.5 to 5.7% with positive control materials and 7.2 to 10.2% with negative control materials. The agreement between the results of the Elecsys, Architect, Vitros, and Access CLIAs ranged from 94.5 to 98.1%. The clinical sensitivity of all CLIAs was 100%. Each CLIA showed excellent reproducibility and clinical sensitivity. The Elecsys, Architect, Vitros, and Access CLIAs showed clinical specificities of 98.2, 98.8, 96.5, and 98.2%.
Determination of the copy number of the survival motor neuron (SMN) gene is important for detecti... more Determination of the copy number of the survival motor neuron (SMN) gene is important for detecting spinal muscular atrophy (SMA) carriers and compound heterozygous patients. Multiplex ligationdependent probe amplification (MLPA) assay is a simple and efficient technique used for detecting variations in the copy numbers of different genes. Race- and ethnicity-based variation in the SMA carrier frequency and the '2+0' genotype of SMN1 are important factors that should be considered when estimating the risk of being an SMA carrier. Since SMN2 plays a disease-modifying role, accurate determination of SMN2 copy numbers in SMA patients can serve as a useful prognostic tool. Therefore, information on the SMN2 genotype distributions in normal populations will be helpful in selecting appropriate reference samples for MLPA analysis. To determine SMA carrier frequencies and SMN genotype distribution, we determined the copy numbers of SMN1 and SMN2 genes using the MLPA assay in 100 unrelated Korean individuals with no family history of SMA. The frequency of SMA carriers in the Korean population appears to be 1 in 50, which indicates that the prevalence of SMA among Koreans is the same as that among individuals in the Western countries. Two of the 100 normal individuals enrolled in this study showed 3 copies of the SMN1 gene. Therefore, 1.0% of the 198 normal alleles in this population was estimated to be 2-copy alleles ('2+0' genotype). SMN2 copy numbers showed a high degree of individual variation. Our results showed that 64% of the individuals had 2 copies of SMN2, but 36% individuals had between 0, 1, or 3 copies of the gene.
Hereditary nonpolyposis colorectal cancer (HNPCC) (MIM #114500), also called Lynch syndrome, is a... more Hereditary nonpolyposis colorectal cancer (HNPCC) (MIM #114500), also called Lynch syndrome, is an autosomal dominantly inherited cancer syndrome accounting for 1-5% of all colorectal cancer cases. In a study of three Korean families with HNPCC consistent with the revised Bethesda criteria, DNA testing revealed three novel HNPCC germline mutations in two genes: namely, MLH1, with an insertion resulting in a frameshift and a premature stop codon; MSH2, with a deletion at nucleotide 633, exon 3, which results in stop of translation at codon 213; and MSH2, with a deletion at nucleotide 1413, exon 9, resulting in a frameshift and a premature stop codon. In the first two families, there were splice mutations at c.2006-6 thymine to cytosine. The clinical implications of a frameshift mutation are discussed, along with the significance of common underlying splice mutations existing within families with HNPCC.
A rare karyotypic event, der(1;15)(q10;q10), which involves the whole long arms of chromosomes 1 ... more A rare karyotypic event, der(1;15)(q10;q10), which involves the whole long arms of chromosomes 1 and 15, has been reported in patients with various conditions, including acute myelogenous leukemia, myelodysplastic syndrome, polycythemia vera, and multiple myeloma. Only 27 cases of unbalanced der(1;15)(q10;q10) have been documented in the literature as single or complexed chromosomal abnormalities in hematological malignancies. Here, we describe two cases of acute lymphoblastic leukemia with der(1;15)(q10;q10), and review the previous reports. Although more case studies are needed, we suggest that der(1;15)(q10;q10) should be considered a nonrandom chromosomal abnormality in hematological malignancies including both lymphoid and myeloid neoplasms.
We report the case of a 38-year-old man with acute promyelocytic leukemia (APL) showing a distinc... more We report the case of a 38-year-old man with acute promyelocytic leukemia (APL) showing a distinct breakpoint cluster region 2 (bcr2) variant transcript. Findings from bone marrow, cytogenetic, fluorescence in situ hybridization, and qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were consistent with the diagnosis of APL. Although PCR products of size 841 bp and 984 bp were amplified from bone marrow specimen, the quantitative PCR (RQ-PCR) findings were negative. Given the discrepancy in PCR results, sequencing of PCR products was performed to determine the detailed composition of these fusion transcripts. By cloning and sequencing, we discovered that these two bands were isoforms, in which one exon (exon 5, 144 bp) of the PML gene was spliced out of the smaller products (minor PCR products); one sequence (G) insertion and one base substitution (T-->C) of PML exon 4 generate a stop codon in the smaller fusion transcript. In addition, a search of the Ensembl database revealed that these variant PML/RARA fusion transcripts were composed of exon 7a insertion of the PML gene and partial deletion (46 bp) of exon 3 of the RARA gene, in addition to inserted sequences of intron 7 of PML and genomic sequence ATCT of unknown origin at the fusion junction site. Although the biological significance of most atypical transcripts remains unclear, sequence analysis of these atypical products should be performed, to reveal the composition of such a fusion transcript and elucidate the molecular mechanism.
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Papers by seoyoung yoon