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Determination of SMN1 and SMN2 Copy Numbers in a Korean Population using Multiplex Ligation-dependent Probe Amplification.

Seoyoung YOON ; Chang Hoon LEE ; Kyung A LEE

The Korean Journal of Laboratory Medicine.2010;30(1):93-96. doi:10.3343/kjlm.2010.30.1.93

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.
Asian Continental Ancestry Group/*genetics ; *Gene Dosage ; Heterozygote ; Humans ; Muscular Atrophy, Spinal/*genetics ; Nucleic Acid Amplification Techniques ; Republic of Korea ; Survival of Motor Neuron 1 Protein/*genetics ; Survival of Motor Neuron 2 Protein/*genetics

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Recombinant Chromosome 4 with Partial 4p Deletion and 4q Duplication Inherited from Paternal Pericentric Inversion.

Se Jin MUN ; Eun Hae CHO ; Myoung Jae CHEY ; Gyu Hong SHIM ; Bo Moon SHIN ; Rae Kyung LEE ; Ji Kyung KO ; Soo Jin YOO

The Korean Journal of Laboratory Medicine.2010;30(1):89-92. doi:10.3343/kjlm.2010.30.1.89

Pericentric inversion of chromosome 4 can give rise to 2 alternate recombinant (rec) chromosomesby duplication or deletion of 4p. The deletion of distal 4p manifests as Wolf-Hirschhorn syndrome (WHS). Here, we report the molecular cytogenetic findings and clinical manifestations observed in an infant with 46,XX,rec(4)dup(4q)inv(4)(p16q31.3)pat. The infant was delivered by Cesarean section at the 33rd week of gestation because pleural effusion and polyhydramnios were detected on ultrasonography. At birth, the infant showed no malformation or dysfunction, except for a preauricular skin tag. Array comparative genomic hybridization analysis of neonatal peripheral blood samples showed a gain of 38 Mb on 4q31.3-qter and a loss of 3 Mb on 4p16.3, and these results were consistent with WHS. At the last follow-up at 8 months of age (corrected age, 6 months), the infant had not achieved complete head control.
*Chromosome Deletion ; *Chromosome Duplication ; *Chromosome Inversion ; *Chromosomes, Human, Pair 4 ; Comparative Genomic Hybridization ; Female ; Gestational Age ; Humans ; Infant ; Pleural Effusion/ultrasonography ; Polyhydramnios/ultrasonography ; Pregnancy ; Wolf-Hirschhorn Syndrome/*genetics

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A de novo Proximal 6q Deletion Confirmed by Array Comparative Genomic Hybridization.

Kwang Sook WOO ; Ji Eun KIM ; Kyung Eun KIM ; Myo Jing KIM ; Jae Ho YOO ; Hyun Sook AHN ; Lisa G SHAFFER ; Jin Yeong HAN

The Korean Journal of Laboratory Medicine.2010;30(1):84-88. doi:10.3343/kjlm.2010.30.1.84

Deletions of chromosome 6q, particularly in the proximal region, are relatively rare. Here, we report on a de novo interstitial deletion of (6)(q13q16.2) in a girl with facial dysmorphism, congenital hip dislocation, porencephaly, and brain atrophy. Array comparative genomic hybridization analysis showed arr 6q13q16.2(73,378,824-99,824,130), demonstrating higher resolution than the conventional cytogenetic findings, del(6)(q12q15). The clinical data were analyzed and compared with those of similar patients previously reported in the literature.
Abnormalities, Multiple/*genetics ; *Chromosome Deletion ; *Chromosomes, Human, Pair 6 ; Comparative Genomic Hybridization/*methods ; Female ; Humans ; Infant, Newborn ; Karyotyping ; Oligonucleotide Array Sequence Analysis

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Estrogen receptor 1, Glutathione S-transferase P1, Glutathione S-transferase M1, and Glutathione S-transferase T1 Genes with Dysmenorrhea in Korean Female Adolescents.

Hee Yeon WOO ; Kye Hyun KIM ; Se Won LIM

The Korean Journal of Laboratory Medicine.2010;30(1):76-83. doi:10.3343/kjlm.2010.30.1.76

BACKGROUND: Dysmenorrhea is the most common gynecologic complaint among adolescent females. We investigated the association between genetic polymorphisms and dysmenorrhea. METHODS: A total of 202 postmenarcheal Korean female adolescents 16-17 yr old participated in this study. Genotyping for glutathione S-transferase mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1), glutathione S-transferase pi 1 (GSTP1), and estrogen receptor 1 (ESR1) was performed using PCR-based methods. RESULTS: The PP+Pp genotype of the ESR1 gene was more frequent than pp genotypes in subjects with dysmenorrhea than in subjects without dysmenorrhea (odds ratio=2.440; 95% confidence interval, 1.036-5.753; P=0.040) using an unadjusted univariate logistic regression analysis. The relationship between dysmenorrhea and ESR1 gene polymorphisms remained significant after adjustment for premenstrual syndrome, years elapsed after menarche, and family history of dysmenorrhea. No significant difference was observed between subjects with dysmenorrhea and subjects without dysmenorrhea for polymorphisms of GSTM1, GSTT1, and GSTP1 genes. CONCLUSIONS: Our results suggest that ESR1 gene polymorphisms may be associated with dysmenorrhea.
Adolescent ; Asian Continental Ancestry Group/genetics ; Dysmenorrhea/*genetics ; Estrogen Receptor alpha/*genetics ; Female ; Genotype ; Glutathione S-Transferase pi/*genetics ; Glutathione Transferase/*genetics ; Humans ; Logistic Models ; Odds Ratio ; Polymorphism, Genetic ; Republic of Korea

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Identification of a Novel Deletion Region in 3q29 Microdeletion Syndrome by Oligonucleotide Array Comparative Genomic Hybridization.

Eul Ju SEO ; Kyung Ran JUN ; Han Wook YOO ; Hanik K YOO ; Jin Ok LEE

The Korean Journal of Laboratory Medicine.2010;30(1):70-75. doi:10.3343/kjlm.2010.30.1.70

BACKGROUND: The 3q29 microdeletion syndrome is a genomic disorder characterized by mental retardation, developmental delay, microcephaly, and slight facial dysmorphism. In most cases, the microdeletion spans a 1.6-Mb region between low-copy repeats (LCRs). We identified a novel 4.0- Mb deletion using oligonucleotide array comparative genomic hybridization (array CGH) in monozygotic twin sisters. METHODS: G-banded chromosome analysis was performed in the twins and their parents. Highresolution oligonucleotide array CGH was performed using the human whole genome 244K CGH microarray (Agilent Technologies, USA) followed by validation using FISH, and the obtained results were analyzed using the genome database resources. RESULTS: G-banding revealed that the twins had de novo 46,XX,del(3)(q29) karyotype. Array CGH showed a 4.0-Mb interstitial deletion on 3q29, which contained 39 genes and no breakpoints flanked by LCRs. In addition to the typical characteristics of the 3q29 microdeletion syndrome, the twins had attention deficit-hyperactivity disorder, strabismus, congenital heart defect, and gray hair. Besides the p21-activated protein kinase (PAK2) and discs large homolog 1 (DLG1) genes, which are known to play a critical role in mental retardation, the hairy and enhancer of split 1 (HES1) and antigen p97 (melanoma associated; MFI2) genes might be possible candidate genes associated with strabismus, congenital heart defect, and gray hair. CONCLUSIONS: The novel 4.0-Mb 3q29 microdeletion found in the twins suggested the occurrence of genomic rearrangement mediated by mechanisms other than nonallelic homologous recombination. Molecular genetic and functional studies are required to elucidate the contribution of each gene to a specific phenotype.
Adaptor Proteins, Signal Transducing/genetics ; Adolescent ; Attention Deficit Disorder with Hyperactivity/genetics ; Basic Helix-Loop-Helix Transcription Factors/genetics ; *Chromosome Deletion ; Chromosome Disorders/*genetics ; *Chromosomes, Human, Pair 3 ; Comparative Genomic Hybridization/*methods ; Diseases in Twins/*genetics ; Female ; Homeodomain Proteins/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Melanoma-Specific Antigens/genetics ; Membrane Proteins/genetics ; Oligonucleotide Array Sequence Analysis ; Syndrome ; Twins ; p21-Activated Kinases/genetics

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The M142T Mutation Causes B3 Phenotype: Three Cases and an in vitro Expression Study.

Duck CHO ; Dong Jun SHIN ; Mark Harris YAZER ; Chun Hwa IHM ; Young Moon HUR ; Seung Jung KEE ; Soo Hyun KIM ; Myung Geun SHIN ; Jong Hee SHIN ; Soon Pal SUH ; Dong Wook RYANG

The Korean Journal of Laboratory Medicine.2010;30(1):65-69. doi:10.3343/kjlm.2010.30.1.65

The B3 phenotype is the most common B subtype in Korea. The B305 allele (425 T>C, M142T) was first reported in 2 Chinese individuals; however, it has not yet been reported in the Koreans, and the impact of the M142T mutation on the expression of the B3 phenotype has also not been studied. To resolve an ABO discrepancy between a group O neonate and her group O father and A(1)B(3) mother, blood samples from these individuals and other family members were referred to our laboratory for ABO gene analysis. The B305 allele was discovered in the neonate (B305/O01), her mother (A102/ B305), and her maternal aunt (B305/O02), while her father was typed as O01/O02. Transient transfection experiments were performed in HeLa cells using the B305 allele synthesized by site-directed mutagenesis; flow cytometric analysis revealed that this transfect expressed 35.5% of the total B antigen produced by the B101 allele transfect. For comparison, Bx01 allele transfects were also created, and they expressed 11.4% of the total B antigen expressed on the surface of B101 transfects. These experiments demonstrate that the M142T (425 T>C) mutation is responsible for the B subtype phenotype produced by the B305 allele.
ABO Blood-Group System/*genetics ; Adult ; Alleles ; *Amino Acid Substitution ; Child ; Female ; Flow Cytometry ; Gene Expression Regulation ; Genotype ; Hela Cells ; Humans ; *Mutation ; Phenotype ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Transfection

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Investigation of the Prevalence of Human Parvovirus B19 DNA in Korean Plasmapheresis Donors.

Deok Ja OH ; Yoo La LEE ; Jae Won KANG ; So Yong KWON ; Nam Sun CHO

The Korean Journal of Laboratory Medicine.2010;30(1):58-64. doi:10.3343/kjlm.2010.30.1.58

BACKGROUND: To ensure the safety of plasma derivatives, some countries have been screening for the human parvovirus B19 (B19V) antigen or DNA in blood donors. We investigated the prevalence of B19V DNA and anti-B19V antibodies in Korean plasmapheresis donors to evaluate the necessity of B19V DNA screening test. METHODS: Plasma samples were collected between March and July 2008 from 10,032 plasmapheresis donors. The B19V DNA test was performed using the LightCycler 2.0 (Roche, Germany) with quantification kits. Anti-B19V IgM and IgG were tested in 928 randomly selected samples from the 10,032 donors using recomWell Parvovirus B19 ELISA IgM, IgG assay (Mikrogen, Germany). RecomLine Parvovirus B19 LIA IgG, IgM assay (Mikrogen, Germany) was used to analyze the epitopes of antibodies in donors showing positive results for B19V DNA and anti-B19V antibodies. DNA sequencing was performed to identify the genotypes. RESULTS: The prevalence of B19V DNA was 0.1% (10/10,032). Virus titers in B19V DNA positive donors were less than 10(5) IU/mL (range: 2.7x10(1)-3.2x10(4) IU/mL) except for 1 donor (1.33x10(8) IU/mL). All the isolated B19V DNAs from 6 donors were identified as genotype I. Nine out of 10 B19V DNA positive donors also possessed anti-B19V IgG only or IgG and IgM. The prevalence of anti-B19V IgG was 60.1% (558/928). CONCLUSIONS: The prevalence of B19V DNA in Korean blood donors was not high and most donors also possessed neutralizing anti-B19V antibodies. Thus, the implementation of a B19V screening test for Korean blood donors does not appear to be imperative.
Adolescent ; Adult ; Aged ; Antibodies, Viral/blood ; *Blood Donors ; DNA, Viral/*blood ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; Follow-Up Studies ; Genotype ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Male ; Middle Aged ; Parvoviridae Infections/epidemiology ; Parvovirus B19, Human/genetics/immunology/*isolation & purification ; *Plasmapheresis ; Polymerase Chain Reaction/methods ; Prevalence ; Republic of Korea/epidemiology ; Retrospective Studies

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The Relationship between Lewis/Secretor Genotypes and Serum Carbohydrate Antigen 19-9 Levels in a Korean Population.

Hyung Doo PARK ; Kyoung Un PARK ; Junghan SONG ; Chang Seok KI ; Kyou Sup HAN ; Jin Q KIM

The Korean Journal of Laboratory Medicine.2010;30(1):51-57. doi:10.3343/kjlm.2010.30.1.51

BACKGROUND: The Lewis histo-blood group system consists of 2 major antigens-Lea and Leb-and a sialyl Lewis antigen-carbohydrate antigen (CA) 19-9. We investigated the distribution of Lewis genotypes and evaluated the relationship between the Lewis/Secretor genotypes and the serum level of CA 19-9 in a Korean population to identify whether the serum CA 19-9 levels are influenced by the Lewis/Secretor genotypes. METHODS: The study included 242 individuals who had no malignancies. Lewis genotyping was performed for the 59T>G, 508G>A and 1067T>A polymorphic sites. The Secretor genotype was determined through analysis of the 357C>T and 385A>T polymorphic sites and the fusion gene. Serum CA 19-9 level was analyzed using an electrochemiluminescence immunoassay. RESULTS: Individuals carrying the 3 common genotypes-Le/Le, Le/le(59,508), and Le/le(59,1067)-accounted for 95% of the study population. In the Korean population, the allelic frequencies of Le, Le(59), le(59,508), and le(59,1067) were 0.731, 0.010, 0.223, and 0.035, respectively. We found a significant difference in serum CA 19-9 concentrations among the 9 Lewis/Secretor genotype groups (P<0.001). The serum CA 19-9 levels in subjects with genotype groups 1 and 2 (Le/- and se/se) were higher than those with genotype groups 3-6 (Le/- and Se/-; 15.63 vs 6.64 kU/L, P<0.001). CONCLUSIONS: Le/Le, Le/le(59,508), and Le/le(59,1067) are frequent Lewis genotypes in Koreans. Because serum CA 19-9 levels are significantly influenced by the Lewis/Secretor genotypes, caution is suggested when interpreting the serum CA 19-9 levels.
Adult ; Aged ; Alleles ; Asian Continental Ancestry Group/*genetics ; CA-19-9 Antigen/*blood ; Chemiluminescent Measurements/methods ; Female ; Gene Frequency ; Genotype ; Humans ; Immunoassay/methods ; Lewis Blood-Group System/*genetics ; Male ; Middle Aged ; Phenotype ; Polymorphism, Genetic ; Republic of Korea

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Evaluation of the Virus-elimination Efficacy of Nanofiltration (Viresolve NFP) for the Parvovirus B19 and Hepatitis A Virus.

Deok Ja OH ; Yoo La LEE ; Jae Won KANG ; So Yong KWON ; Nam Sun CHO ; In Seop KIM

The Korean Journal of Laboratory Medicine.2010;30(1):45-50. doi:10.3343/kjlm.2010.30.1.45

BACKGROUND: The safety of plasma derivatives has been reinforced since 1980s by variable pathogen inactivation or elimination techniques. Nucleic acid amplification test (NAT) for the source plasma has also been implemented worldwide. Recently nanofiltration has been used in some country for ensuring safety of plasma derivatives to eliminate non-enveloped viruses such as parvovirus B19 (B19V) and hepatitis A virus (HAV). We evaluated the efficacy of nanofiltration for the elimination of B19V and HAV. METHODS: To verify the efficacy of nanofiltration, we adopted a 20 nm Viresolve NFP (Millipore, USA) in the scaling down (1:1,370) model of the antithrombin III production. As virus stock solutions, we used B19V reactive plasma and porcine parvovirus (PPV) and HAV obtained from cell culture. And 50% tissue culture infectious dose was consumed as infectious dose. The methods used to evaluate the virus-elimination efficacy were reverse-transcriptase polymerase chain reaction for B19V and the cytopathic effect calculation after filtration for PPV and HAV. RESULTS: B19V was not detected by RT-PCR in the filtered antithrombin III solutions with initial viral load of 6.42x10(5) IU/mL and 1.42x10(5) IU/mL before filtration. The virus-elimination efficacy of nanofiltration for PPV and HAV were > or =10(3.32) and > or =10(3.31), respectively. CONCLUSIONS: Nanofiltration would be an effective method for the elimination of B19V and HAV. It may be used as a substitute for NAT screening of these viruses in source plasma to ensure safety of plasma derivatives in Korea.
Antithrombin III/isolation & purification ; DNA, Viral/analysis ; Filtration/*methods ; Hepatitis A virus/genetics/*isolation & purification ; Humans ; Nanotechnology/*methods ; Parvovirus B19, Human/genetics/*isolation & purification ; RNA, Viral/analysis ; Reverse Transcriptase Polymerase Chain Reaction

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Prevalence and Clinical Associations of Lupus Anticoagulant, Anticardiolipin Antibodies, and Anti-beta2-glycoprotein I Antibodies in Patients with Systemic Lupus Erythematosus.

Kwang Sook WOO ; Kyung Eun KIM ; Jeong Man KIM ; Jin Yeong HAN ; Won Tae CHUNG ; Kyeong Hee KIM

The Korean Journal of Laboratory Medicine.2010;30(1):38-44. doi:10.3343/kjlm.2010.30.1.38

BACKGROUND: The presence of antiphospholipid antibodies (aPLs) is associated with the clinical features of antiphospholipid syndrome (APS), which comprises venous and arterial thrombosis and pregnancy loss, and systemic lupus erythematosus (SLE). The prevalence of aPLs has been reported to be different in patient populations affected by either of these conditions. We performed a retrospective study to evaluate the prevalence and clinical associations of aPLs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) in a cohort of Korean patients with SLE. METHODS: This study included samples from 88 SLE patients for whom aPL testing had been advised between June 2006 and July 2009 at the Dong-A University Hospital. Serum and plasma samples were tested for LAC, aCL (IgG, IgM), and anti-beta2-GPI (IgG, IgM) antibodies. Clinical data from patients were obtained from a review of medical records. RESULTS: LAC was the most common (34.1% of total patients, 30/88) antibody, followed by IgM aCL (31.8%, 28/88), IgG aCL (18.2%, 16/88), and IgM and IgG anti-beta2-GPI (both 5.7%, 5/88 each). Positivity for LAC was strongly associated with venous/arterial thrombosis (P=0.002). CONCLUSIONS: LAC was the most common antibody detected in Korean SLE patients and is shown to have a significant association with the presence of venous/arterial thrombosis. The measurement of LAC may be clinically useful in identifying patients with SLE who are at a high risk for venous/arterial thrombosis.
Adolescent ; Adult ; Antibodies, Anticardiolipin/*blood ; Antibodies, Antiphospholipid/*blood ; Cohort Studies ; Female ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Lupus Coagulation Inhibitor/*blood ; Lupus Erythematosus, Systemic/epidemiology/*immunology ; Male ; Middle Aged ; Pregnancy ; Prevalence ; Retrospective Studies ; Risk Factors ; Venous Thrombosis/epidemiology/immunology

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