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Unbalanced translocation der(8)t(8:13)(p23.3;q32.1)dn identified by array CGH and subtelomeric FISH in a patient with mental retardation.

Soomin LEE ; Dongsuk LEE ; Hyunah JEONG ; Kichul KIM ; Doyeong HWANG

Journal of Genetic Medicine.2008;5(1):65-68.

Molecular cytogenetics allows the identification of unknown chromosome rearrangements, which is clinically useful in patients with mental retardation and/or development delay. We report on a 31-year- old woman with severe mental retardation, behavior development delay, and verbal performance delay. Conventional cytogenetic analysis showed a 46,XX,add(8)(p23.3) karyotype. To determine the origin of this unbalanced translocation, we performed array CGH and subtelomeric FISH. The results showed that the distal region of chromosome 8p was added to the terminal of chromosome 13q. This was confirmed the final result of 46,XX,der(8)t(8:13)(p23.3;q32.1)dn.
Cytogenetic Analysis ; Cytogenetics ; Female ; Humans ; Intellectual Disability ; Karyotype

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Pseudoisodicentric X chromosome in a female with primary amenorrhea.

Sang Hee PARK ; Sung Han SHIM ; Mi Uk CHIN ; Su Jin KANG ; Sung Mi BAE ; Soo Min SOHN ; Dong Hyun CHA ; Tae Ki YOON ; Jung Hyun CHO

Journal of Genetic Medicine.2008;5(1):61-64.

A 24-year-old female with primary amenorrhea was referred for a chromosome study. The karyotype of the patient was 46,X,der(X) under initial GTG-banding analysis. Fluorescence in situ hybridization (FISH) analysis with an LSI Kallmann (KAL) region probe [probes for Xp22.3(KAL) and CEP(X) for control] was carried out. The abnormal chromosome was KAL- and CEP(X)x2. In addition, interphase FISH analysis revealed the patient to be mosaic for two different cell lines: 90% of cells had three signals and 10% of the cells had only one signal for CEP(X). Based on these results, the karyotype of the patient was 45,X/46,X,psu idic(X)(p22.1), which is partial trisomy for Xqter-->Xp22.1 and partial monosomy for Xpter-->Xp22.1. This karyotype was considered a variant of Turner syndrome. In summary, Idic(X) and low-level mosaicism was successfully characterized by FISH analysis with a CEP(X) probe.
Amenorrhea ; Chromosome Deletion ; Female ; Fluorescence ; Humans ; In Situ Hybridization ; Interphase ; Karyotype ; Mosaicism ; Trisomy ; Turner Syndrome ; X Chromosome ; Young Adult

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Karyotype analysis of cryopreserved mononuclear cells from cord blood.

Ki Young KU ; Mi Ae CHU ; Ji Yoon KIM ; Kun Soo LEE

Journal of Genetic Medicine.2008;5(1):55-60.

PURPOSE: The ability to perform chromosome analysis of cryopreserved cord blood mononuclear cells is important for future retrospective studies. We compared the karyotypes of cryopreserved cells with cells before cryopreservation. METHODS: One cord blood (CB) sample was obtained from normal healthy volunteer. Karyotype analysis was performed before cryopreservation. After mononuclear cell separation with Ficoll-Hypaque, the mononuclear cells were cryopreserved by programmed controlled-rate freezer and then transferred into the liquid nitrogen (-196 degrees C) for 3 days. After rapid thawing, cytogenetic analysis was performed as the same method for each sample by different conditions. The samples were divided by three groups. The first group was no culture before cryopreservation, the second group was 72 hours culture before cryopreservation, but no 24 hours culture after thawing and the third group was 72 hours culture before cryopreservation and 24 hours culture after thawing. RESULTS: The chromosome analysis was successful in the second and third groups of CB sample. CONCLUSION: The successful result from CB samples may suggest the usefulness of long-term cryopreservation for retrospective study in various clinical settings including hematologic malignancies.
Cell Separation ; Cryopreservation ; Cytogenetic Analysis ; Fetal Blood ; Karyotype ; Nitrogen ; Retrospective Studies

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Rapid prenatal diagnosis of chromosome aneuploidies in 943 uncultured amniotic fluid samples by fluorescence in situ hybridization (FISH).

Sung Hee HAN ; Jeom Soon KANG ; Jeong Wook AN ; Anna LEE ; Young Ho YANG ; Kyu Pum LEE ; Kyoung Ryul LEE

Journal of Genetic Medicine.2008;5(1):47-54.

PURPOSE: Fluorescence in situ hybridization (FISH) on uncultured amniotic fluid cells offers the opportunity for rapid screening of aneuploidies and has become an integral part of the current practice in many clinical cytogenetics laboratories. Here, we retrospectively analyzed the results of interphase FISH in 943 amniotic fluid samples and assessed the efficiency of FISH for rapid detection of aneuploidies. METHODS: Interphase FISH for chromosome 13, 18, and 21 was performed in 943 consecutive amniotic fluid samples for rapid diagnosis of aneuploidies referred from 2004 to 2006. Karyotypes from standard cytogenetic analysis were compared to the FISH results. RESULTS: A total of 45 chromosomal rearrangements (4.8%) were found after conventional cytogenetic analysis of the 943 amniotic fluid. After exclusion of known familiar chromosomal rearrangements and inversions (2.1%, 20/943), 2.7% (25/943) were found to have chromosomal abnormalities. Of this group, 0.7% (6/943) were chromosomal abnormalities not detectable by FISH and 2.0% (19/943) were numerical abnormalities detectable by FISH. All 14 cases of Down syndrome (Classic type, 13 cases; Robertsonian type, 1 case) and 5 cases of trisomy 18 were diagnosed and detected by FISH and there were no false-positive or -negative results (specificity and sensitivity=100%). CONCLUSION: The present study demonstrates that FISH can provide a rapid and sensitive clinical method for prenatal identification of chromosome aneuploidies. However, careful genetic counseling is essential to explain the limitations of FISH, including the inability to detect all chromosomal abnormalities and the possibilities of uninformative or false-negative results in some cases.
Amniocentesis ; Amniotic Fluid ; Aneuploidy ; Chromosome Aberrations ; Chromosomes, Human, Pair 13 ; Cytogenetic Analysis ; Cytogenetics ; Down Syndrome ; Female ; Fluorescence ; Genetic Counseling ; In Situ Hybridization ; Interphase ; Karyotype ; Mass Screening ; Prenatal Diagnosis ; Retrospective Studies ; Trisomy

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Molecular diagnosis of fragile X syndrome in a female child.

Seon Yong JEONG ; Jeong A YANG ; Hyon J KIM

Journal of Genetic Medicine.2008;5(1):41-46.

PURPOSE: Fragile X syndrome (FXS) is the most common heritable cause of cognitive impairment. FXS is caused by hyperexpansion and hypermethylation of a polymorphic CGG trinucleotide repeat in the 5' untranslated region of the fragile X mental retadation-1(FMR1) gene. Combination of Southern blotting and simple polymerase chain reaction(PCR) amplification of the FMR1 repeat region is commonly used for diagnosis in females. To give a definite diagnosis in a female child suspected of having FXS, we carried out the molecular diagnostic test for FXS using the recently developed Abbott Molecular Fragile X PCR Kit. METHODS: The PCR amplification of the FMR1 repeat region was performed using the Abbott Mdecular Fragile X PCR Kit. The amplified products were analyzed by size-separate analysis on 1.5% agarose gels and by DNA fragment analysis using Gene scan. RESULTS: Agarose gel and Gene scan analyses of PCR products of the FMR1 repeat region showed that the patient had two heterozygous alleles with a normal 30 repeats and full mutation of >200 repeats whereas her mother had two heterozygous alleles with the normal 30 repeats and premutation of 108 repeats, suggesting that the premutation of 108 repeats in her mother may have led to the full mutation of >200 repeats in the patient. CONCLUSION: We diagnosed FXS in a female patient using a simplified molecular diagnostic test. This commercially available diagnostic test for FXS, based on PCR, may be a suitable alternative or complement method to Southern blot analysis and PCR analysis and/or methylation specific(MS)-PCR analysis for the molecular diagnosis of FXS in both males and females.
5' Untranslated Regions ; Alleles ; Blotting, Southern ; Child ; Complement System Proteins ; Diagnostic Tests, Routine ; DNA ; Female ; Fragile X Syndrome ; Gels ; Humans ; Male ; Methylation ; Mothers ; Pathology, Molecular ; Polymerase Chain Reaction ; Sepharose ; Trinucleotide Repeats

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No association between endothelin-1 gene polymorphisms and preeclampsia in Korean population.

Shin Young KIM ; So Yeon PARK ; Ji Hyae LIM ; Jae Hyug YANG ; Moon Young KIM ; Hyun Young PARK ; Kwang Soo LEE ; Hyun Mee RYU

Journal of Genetic Medicine.2008;5(1):34-40.

PURPOSE: Preeclampsia is a major cause of maternal and perinatal mortality and morbidity and is considered to be a multifactorial disorder involving a genetic predisposition and environmental factors. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, and alterations in the ET-1 system are thought to play a role in triggering the vasoconstriction seen with preeclampsia. The aim of this study was to examine the frequency of the 4 common single-nucleotide polymorphisms (SNPs) (c.1370T>G, c.137_139delinsA, c.3539+2T>C, and c.5665G>T) of the ET-1 gene in normotensive and preeclamptic pregnancies and to investigate whether these SNPs are associated with preeclampsia in pregnant Korean women. METHODS: We analyzed blood samples from 206 preeclamptic and 216 normotensive pregnancies using a commercially available SNapShot kit and an ABI Prism 3100 Genetic analyzer. RESULTS: There were no significant differences in genotype or allele frequencies of the 4 SNPs in the ET-1 gene between preeclamptic and normotensive pregnancies. The respective frequencies of the 3 haplotypes (TDTG, GDCT, and TICT; >10% haplotype frequency) were 61%, 13% and 13%, respectively, in preeclampsic pregnancies and 62%, 14% and 12%, respectively, in normotensive pregnancies. The frequencies of these haplotypes were similar for both groups. Using multiple logistic regression analysis, we did not observe an increase in the risk of preeclampsia for the 4 SNPs of the ET-1 gene under either a recessive or dominant model. CONCLUSION: This study suggests that the 4 SNPs of the ET-1 gene are not associated with an increased risk for preeclampsia in pregnant Korean women.
Endothelin-1 ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Logistic Models ; Perinatal Mortality ; Polymorphism, Single Nucleotide ; Pre-Eclampsia ; Pregnancy ; Vasoconstriction

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The Study of DNA Mutations of Phenylketonuria in Koreans.

Su Jung YOO ; Yong Hee HONG ; Yong Wha LEE ; Sung Chul JUNG ; Chang Seok KI ; Dong Hwan LEE

Journal of Genetic Medicine.2008;5(1):26-33.

PURPOSE: Phenylketonuria(PKU) is an inborn error of metabolism and a genetic disorder resulting from a deficiency of phenylalanine hydroxylase(PAH) and decreased activity of tetrahydrobiopterin(BH4).In this study the correlation between the DNA mutation and clinical manifestations was investigated and PAH DNA mutations were compared bewteen Asian and Caucasian populations. METHODS: DNA was isolated from peripheral leukocytes. The PAH gene was amplified by Polymerase Chain Reaction(PCR) and the sequence was analyzed with Multiplex Ligation-dependent Probe Amplification(MLPA). RESULTS: We characterized the PAH gene of 102 independent Korean patients with PKU. PAH nucleotide sequence analysis revealed 44 different mutations, including 10 novel mutations comprising 9 missense mutations(N207D, K95del, A447P, G344D, P69S, S391I, A202T, G103S, and I306L) and 1 novel splice-site variant mutation(IVS10-3C>G). R243Q was the most prevalent mutation in this study. A259T has not previously been reported in Asian populations, but we found that this mutation had a frequency of 10.1% in our study. Furthermore, the genotypes of BH4 responsive patients were analyzed and were divided into two groups: BH4 medication-only group and BH4 medication with diet therapy group. In the BH4 medication-only group and BH4 medication with diet therapy group, R241C was the most common mutation. CONCLUSION: Novel mutations in the PAH gene of PKU patients are still being discovered. Additional information as to the frequency of mutations in the tetrahydrobiopterine responsive gene is also accumulating. We anticipate that knowledge of these PKU gene mutations will assist the diagnosis, genetic counseling, and therapeutic treatment of PKU patients in future.
Asian Continental Ancestry Group ; Base Sequence ; DNA ; Genetic Counseling ; Genotype ; Humans ; Leukocytes ; Phenylalanine ; Phenylalanine Hydroxylase ; Phenylketonurias

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Seven-year experience with inherited metabolic disorders screening by tandem mass spectrometry.

Sean Mi SONG ; Hye Ran YOON ; Anna LEE ; Kyoung Ryul LEE

Journal of Genetic Medicine.2008;5(1):21-25.

PURPOSE: In recent years, many countries have adopted newborn screening programs that use tandem mass spectrometry (MS/MS) to screen and the number of diseases screened has also increased. We began screening for inherited metabolic disorders using MS/MS in April, 2001. Our goal was to determine the overall prevalence of metabolic disorders and to assess the effectiveness of newborn screening by MS/MS in Korea. METHODS: From April, 2001 to December, 2007, we screened newborns and high risk groups using MS/MS. Acylcarnitines and amino acids were extracted and butylated and were introduced into the inlet of MS/MS. Confirmatory testing including a repeat newborn screening, and urine organic acid and plasma amino acid analysis were performed on a case-by-case basis. RESULTS: The total number of screened subjects 284,933 which comprised 251,799 neonates and 33,134 high risk subjects. The recall rate was 0.4% (1158 tests) and true positive cases were 117 (0.04%). Confirmed metabolic disorders (newborn/high risk group) were as follows; 78 (25/53) amino acid disorders, 27 (16/11) organic acid disorders, and 12 (5/7) fatty acid oxidation disorders. The estimated prevalence of inherited metabolic diseases in newborns was 1:5,000 and that in the total group was 1:2,000. CONCLUSION: Newborn screening by MS/MS improved the detection of many inherited metabolic disorders. We therefore propose that all newborns be screened by a MS/MS national program and followed-up using a systemic organization strategy.
Amino Acids ; Bays ; Humans ; Infant, Newborn ; Mass Screening ; Metabolic Diseases ; Plasma ; Prevalence ; Tandem Mass Spectrometry

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Diagnostic testing for Duchenne/Becker Muscular dystrophy using Dual Priming Oligonucleotide (DPO) system.

Joo Hyun KIM ; Gu Hwan KIM ; Jin Joo LEE ; Dae Hoon LEE ; Jong Kee KIM ; Han Wook YOO

Journal of Genetic Medicine.2008;5(1):15-20.

PURPOSE: Large exon deletions in the DMD gene are found in about 60% of DMD/BMD patients. Multiplex PCR has been employed to detect the deletion mutation, which frequently generates noise PCR products due to the presence of multiple primers in a single reaction as well as the stringency of PCR conditions. This often leads to a false-negative or false-positive result. To address this problematic issue, we introduced the dual primer oligonucleotide (DPO) system. DPO contains two separate priming regions joined by a polydeoxyinosine linker that results in high PCR specificity even under suboptimal PCR conditions. METHODS: We tested 50 healthy male controls, 50 patients with deletion mutation as deletion-positive patient controls, and 20 patients with no deletions as deletion-negative patient controls using DPO- multiplex PCR. Both the presence and extent of deletion were verified by simplex PCR spanning the promoter region (PM) and 18 exons including exons 3, 4, 6, 8, 12, 13, 17, 19, 43-48, 50-52, and 60 in all 120 controls. RESULTS: DPO-multiplex PCR showed 100% sensitivity and specificity for the detection a deletion. However, it showed 97.1% sensitivity and 100% specificity for determining the extent of deletions. CONCLUSION: The DPO-multiplex PCR method is a useful molecular test to detect large deletions of DMD for the diagnosis of patients with DMD/BMD because it is easy to perform, fast, and cost-effective and has excellent sensitivity and specificity.
Diagnostic Tests, Routine ; Exons ; Humans ; Male ; Methylmethacrylates ; Multiplex Polymerase Chain Reaction ; Muscular Dystrophies ; Noise ; Polymerase Chain Reaction ; Polystyrenes ; Promoter Regions, Genetic ; Sensitivity and Specificity ; Sequence Deletion

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The recent trend of prenatal screening.

Doyeong HWANG

Journal of Genetic Medicine.2008;5(1):7-14.

Twenty years have passed since a prenatal screening for Down syndrome and neural tube defect was applied to obstetric field. The Quad test (AFP, hCG, uE3, Inhibin-A) of the second trimester and the combination test (PAPP-A, hCG, NT) of the first trimester became popular now. The recent trend of prenatal screening is to combine these two screening tests together in order to increase a detection rate of Down syndrome. Three types of screening methods are introduced as follows; integrated test, sequential test and contingent test. In addition to combination of each test, an incorporation of characteristic ultrasound findings of Down syndrome is suggested for its risk calculation. The absence of fetal nasal bone would be a very useful marker especially in the first trimester screening test. According to a change of way calculating risk of Down syndrome, obstetrician's role will be more increased not by passive participation, but by active participation using ultrasound in risk calculation.
Adenine ; Carbamates ; Deoxycytidine ; Down Syndrome ; Drug Combinations ; Female ; Humans ; Mass Screening ; Nasal Bone ; Neural Tube Defects ; Organophosphonates ; Pregnancy ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Prenatal Diagnosis ; Quinolones ; Thiazoles ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

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