• Clinical and Experimental Reproductive Medicine
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• v.29 no.4
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• pp.303-310
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• 2002

Objective s: To estimate the frequency of Y chromosome microdeletions in the Korean population of infertile men and to evaluate the relationship between microdeletion on the Y chromosome and clinical phenotypes of infertile men with idiopathic azoospermia and oligozoospermia. Materials and Methods: Genomic DNA was extracted from blood samples collected from 330 infertile men attending the Infertility Clinic at Samsung Cheil Hospital, Korea. Six sequence tagged sites (STSs) spanning the azoospermia factor (AZF) regions of the Y chromosome were amplified by polymerase chain reactions (PCRs). Results: Microdeletions on Y chromosome were detected in 35 (10.6%) of the 330 infertile men. Most of the microdeletions (91.4%) involved AZFb or AZFc. The high incidence of microdeletions were found in AZFc region (57.1%), but the low in AZFa (8.6%) and AZFb (5.7%). Larger microdeletions involving two or three AZF regions were detected in 28.6% of cases. All patients (6 patients) with deletion of AZFa region showed no germ cell phenotypes, Sertoli cell only syndrome or Leydig cell hyperplasia in histopathologic examinations. Conclusion: Microdeletions on the Y chromosome, especially, at AZFc/DAZ regions may be the major cause of azoospermia and severe oligozoospermia. We suggest that idiopathic infertile men have genetic counselling and microdeletion analysis on the Y chromosome before IVF-ET and ART program.

• Clinical and Experimental Pediatrics
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• v.45 no.7
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• pp.917-922
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• 2002

An unbalanced translocation is frequently the result of inheritance of an unbalanced haploid set from a parent with a balanced translocation. Families in which one parent is a balanced translocation carrier fall into the following classes : Those in which none of the possible abnormal offsprings is viable; Those in which one type of offspring, usually the one with the smaller deletion, is born alive; Those in which two types of abnormal offspring are viable. We report a neonate whose karyotype was 46,XX,der(2)t(2;7)(q21;p21.2),der(20)t(2;20)(q21;p13). She was small for her gestational age and had multiple anomalies such as exophthalmos, corneal opacity, short neck, tongue tie, clinodactyly, atrial septal defect, patent ductus arteriosus and ventriculomegaly. Moreover, her mother's karyotype was 46,XX,der(2)t(2;7)(q21;p21.2),del(16)(q22.1),der(20)t(2;20)(q21;p13) but her father had normal karyotype. The same derivative chrosomes were found between mother and her infant, except for del(16)(q22.1) in her mother and these same unbalanced translocations in a two-generation family are extremely rare.

• Genomics & Informatics
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• v.1 no.2
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• pp.101-107
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• 2003

Loss of heterozygosity (LOH) has been used to detect deleted regions of a specific chromosome in cancer cells. LOH on chromosome 16q has been reported to occur frequently in progressed hepatocellular carcinoma (HCC). Liver tissues from 37 Korean HCC patients were analyzed for LOH by using 25 polymorphic microsatellite markers distributed along 16q. Out of the 37 HCC patients studied, 21 patients (56.8%) showed LOH in various regions of 16q with at least one polymorphic marker. Puring the analysis of these 21 LOH cases, 6 patients showed interstitial LOHs in which the boundary of the LOH region was defined. With two rounds of LOH analysis, five commonly occurring interstitial LOH regions were identified; 16q21-22.1, 16q22.2 - 22.3, 16q22.3, 16q23.2 and 16q23.3 - 24.1. Among the five LOH regions the 16q23.3 - 24.1 region has been reported to be related with chromosome instability. A complete physical map, which covers the 3.2 Mb region of 16q23.3 - 24.1 (D16S402 and D16S486), was constructed to identify novel candidate tumor suppressor genes. We provide the minimally tiling path map consisting of 28 BAC clones. There was one gap between NT_10422.11 and NT_019609.9 of the human genome sequence contig (NCBI sequence build 33, April 29, 2003). This gap can be filled by sequencing the R-1425M20 clone which bridges these sequence contigs.

• Clinical and Experimental Pediatrics
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• v.56 no.6
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• pp.265-268
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• 2013

Wiskott-Aldrich syndrome (WAS) is an inherited X-linked disorder. The WAS gene is located on the X chromosome and undergoes mutations, which affect various domains of the WAS protein, resulting in recurrent infection, eczema, and thrombocytopenia. However, the clinical features and severity of the disease vary according to the type of mutations in the WAS gene. Here, we describe the case of a 4-year-old boy with a history of marked thrombocytopenia since birth, who presented with recurrent herpes simplex infection and late onset of eczema. Examination of his family history revealed that older brother, who died from intracranial hemorrhage, had chronic idiopathic thrombocytopenia. Therefore, we proceeded with genetic analysis and found a new deletion mutation in the WAS gene: c.858delC (p.ser287Leufs$^*21$) as a hemizygous form.

• Proceedings of the KSAR Conference
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• 2001.10a
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• pp.14-17
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• 2001

Positional cloning (map-based cloning) of mutations or genetic variations has been served as an invaluable tool to understand in-vivo functions of genes and to identify molecular components underlying phenotypes of interest. Mice homozygous for the cerebellar deficient folia (cdf) mutation are ataxic, with cerebellar hypoplasia and abnormal lobulation of the cerebellum. In the cdf mutant cerebellum approximately 40% of Purkinje cells are ectopically located within the white matter and the inner granule cell layer (IGL). To identify the cdf gene, a high-resolution genetic map for the cdf-gene-encompassing region was constructed using 1997 F2 mice generated from C3H/HeSnJ-cdf/cdf and CAST/Ei intercross. The cdf gene showed complete linkage disequilibrium with three tightly linked markers D6Mit208, D6Mit359, and D6Mit225. A contig using YAC, BAC, and P1 clones was constructed for the cdf critical region to identify the gene. A deletion in the cdf critical region on chromosome 6 that removes approximately 150kb of DNA was identified. A gene associated with this deletion was identified using cDNA selection. cdf mutant mice with the transgenic copy of the identified gene restored the brain abnormalities of the mutant mice. The positional cloning of cdf gene provides a good example showing the identification of a gene could lead to finding a new component of important molecular pathways.

• Journal of Genetic Medicine
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• v.18 no.1
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• pp.31-37
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• 2021

Purpose: To summarize the results of chromosomal microarray analysis (CMA) for copy number variants (CNVs) detection and clinical utility in a single tertiary hospital. Materials and Methods: We performed CMA in 46 patients over the course of two years. Detected CNVs were classified into five categories according to the American College of Medical Genetics and Genomics guidelines and correlated with clinical manifestations. Results: A total of 31 CNVs were detected in 19 patients, with a median CNV number per patient of two CNVs. Among these, 16 CNVs were classified as pathogenic (n=3) or likely pathogenic (LP) (n=11) or variant of uncertain significance (n=4). The 16p11.2 deletion and 16p13.11 deletion classified as LP were most often detected in 6.5% (3/46), retrospectively. CMA diagnostic yield was 24.3% (9/37 patients) for symptomatic patients. The CNVs results of the commercial newborn screening test using next generation sequencing platforms showed high concordance with CMA results. Conclusion: CMA seems useful as a first-tier test for developmental delay with or without congenital anomalies. However, the classification and interpretation of CMA still remained a challenge. Further research is needed for evidence-based interpretation.

• Annals of Clinical Neurophysiology
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• v.10 no.1
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• pp.66-69
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• 2008

Facioscapulohumeral muscular dystrophy (FSHD), the third most common inherited muscular dystrophy, is an autosomal dominant disease characterized by progressive weakness and wasting of the facial, shoulder-girdle, upper arm, foot extensor, and pelvic girdle muscles. FSHD is caused by contraction of the polymorphic D4Z4 repeat in the subtelomere of chromosome 4q. However, there has been no report of genetically confirmed FSHD in Korea. We report a patient with FSHD who was found to have a deletion of D4Z4 repeat on chromosome 4q35.

• The Journal of Korea Assosiation for Disability and Oral Health
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• v.7 no.2
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• pp.115-118
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• 2011

Angelman syndrome(AS) is a rare genetic neurological disorder. The main clinical characteristics of this syndrome are delayed neuropsychological development, intellectual disability, speech impairment, jerky movements especially hand-lapping, frequent laughter or smiling. AS is a classic example of genetic imprinting in that it is usually caused by deletion or inactivation of genes on the maternally inherited chromosome 15. The syndrome has oral manifestations such as diastemas, tongue thrusting, sucking/swallowing disorder, mandibular prognathism, frequent drooling, and excessive chewing behavior. The purpose of this paper is to describe the interesting aspects of the dental treatment of a childe with AS.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.25-28
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• 2016

Phelan-McDermid syndrome is a rare genetic disorder caused by the terminal or interstitial deletion of the chromosome 22q13.3. Patients with this syndrome usually have global developmental delay, hypotonia, and speech delays. Several putative genes such as the SHANK3, RAB, RABL2B, and IB2 are responsible for the neurological features. This study describes the clinical features and outcomes of Korean patients with Phelan-McDermid syndrome. Two patients showing global developmental delay, hypotonia, and speech delay were diagnosed with Phelan-McDermid syndrome via chromosome analysis, fluorescent in situ hybridization, and multiplex ligation-dependent probe amplification analysis. Brain magnetic resonance imaging of Patients 1 and 2 showed delayed myelination and severe communicating hydrocephalus, respectively. Electroencephalography in patient 2 showed high amplitude spike discharges from the left frontotemporoparietal area, but neither patient developed seizures. Kidney ultrasonography of both the patients revealed multicystic kidney disease and pelviectasis, respectively. Patient 2 experienced recurrent respiratory infections, and chest computed tomography findings demonstrated laryngotracheomalacia and bronchial narrowing. He subsequently died because of heart failure after a ventriculoperitoneal shunt operation at 5 months of age. Patient 1, who is currently 20 months old, has been undergoing rehabilitation therapy. However, global developmental delay was noted, as determines using the Korean Infant and Child Development test, the Denver developmental test, and the Bayley developmental test. This report describes the clinical features, outcomes, and molecular genetic characteristics of two Korean patients with Phelan-McDermid syndrome.

• Molecules and Cells
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• v.23 no.1
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• pp.39-48
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• 2007

Charcot-Marie-Tooth (CMT) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are frequent forms of genetically heterogeneous peripheral neuropathies. Reciprocal unequal crossover between flanking CMT1A-REPs on chromosome 17p11.2-p12 is a major cause of CMT type 1A (CMT1A) and HNPP. The importance of a sensitive and rapid method for identifying the CMT1A duplication and HNPP deletion is being emphasized. In the present study, we established a molecular diagnostic method for the CMT1A duplication and HNPP deletion based on hexaplex PCR of 6 microsatellite markers (D17S921, D17S9B, D17S9A, D17S918, D17S4A and D17S2230). The method is highly time-, cost- and sample-saving because the six markers are amplified by a single PCR reaction and resolved with a single capillary in 3 h. Several statistical and forensic estimates indicated that most of these markers are likely to be useful for diagnosing the peripheral neuropathies. Reproducibility, as determined by concordance between independent tests, was estimated to be 100%. The likelihood that genotypes of all six markers are homozygous in randomly selected individuals was calculated to be $1.6{\times}10^{-4}$, which indicates that the statistical error rate for this diagnosis of HNPP deletion is only 0.016%.