• Journal of Genetic Medicine
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• 제17권2호
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• pp.102-107
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• 2020

We report the case of an infant with a 4q35.1 deletion with 10p duplication. This mutation is rarely reported in the literature and has been found to have variable clinical findings, often including developmental delay. In this case, the condition was detected by chromosomal microarray analysis after initial manifestation of a feeding problem and developmental delay. Minor dysmorphic features with abnormal neurological examination led to further evaluation. The father's chromosome complement was 46, XY, t(4;10)(q35;p12.2). Parental balanced translocation can go unrecognized, because affected individuals are often phenotypically healthy until they have fertility issues such as recurrent miscarriages or children with severe congenital disorders. Genetic diagnoses help to establish a clear family genetic background that permits the development of clear treatment strategies. Prenatal counseling can also help to understand the possible risks associated with pregnancy or future child planning.

• Molecules and Cells
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• 제24권2호
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• pp.200-209
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• 2007

We generated gene expression data from the tissues of 50 gastric cancer patients, and applied meta-analysis and gene set analysis to this data and three other stomach cancer gene expression data sets to define the gene expression changes in gastric tumors. By meta-analysis we identified genes consistently changed in gastric carcinomas, while gene set analysis revealed consistently changed biological themes. Genes and gene sets involved in digestion, fatty acid metabolism, and ion transport were consistently down-regulated in gastric carcinomas, while those involved in cellular proliferation, cell cycle, and DNA replication were consistently up-regulated. We also found significant differences between the genes and gene sets expressed in diffuse and intestinal type gastric carcinoma. By gene set analysis of cytogenetic bands, we identified many chromosomal regions with possible gross chromosomal changes (amplifications or deletions). Similar analysis of transcription factor binding sites (TFBSs), revealed transcription factors that may have caused the observed gene expression changes in gastric carcinomas, and we confirmed the overexpression of one of these, E2F1, in many gastric carcinomas by tissue array and immunohistochemistry. We have incorporated the results of our meta- and gene set analyses into a web accessible database (http://human-genome.kribb.re.kr/stomach/).

• Clinical and Experimental Pediatrics
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• 제60권9호
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• pp.282-289
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• 2017

Purpose: Recent advancements in molecular techniques have greatly contributed to the discovery of genetic causes of unexplained developmental delay. Here, we describe the results of array comparative genomic hybridization (CGH) and the clinical features of 27 patients with global developmental delay. Methods: We included 27 children who fulfilled the following criteria: Korean children under 6 years with global developmental delay; children who had at least one or more physical or neurological problem other than global developmental delay; and patients in whom both array CGH and G-banded karyotyping tests were performed. Results: Fifteen male and 12 female patients with a mean age of $29.3{\pm}17.6months$ were included. The most common physical and neurological abnormalities were facial dysmorphism (n=16), epilepsy (n=7), and hypotonia (n=7). Pathogenic copy number variation results were observed in 4 patients (14.8%): 18.73 Mb dup(2)(p24.2p25.3) and 1.62 Mb del(20p13) (patient 1); 22.31 Mb dup(2) (p22.3p25.1) and 4.01 Mb dup(2)(p21p22.1) (patient 2); 12.08 Mb del(4)(q22.1q24) (patient 3); and 1.19 Mb del(1)(q21.1) (patient 4). One patient (3.7%) displayed a variant of uncertain significance. Four patients (14.8%) displayed discordance between G-banded karyotyping and array CGH results. Among patients with normal array CGH results, 4 (16%) revealed brain anomalies such as schizencephaly and hydranencephaly. One patient was diagnosed with Rett syndrome and one with $M{\ddot{o}}bius$ syndrome. Conclusion: As chromosomal microarray can elucidate the cause of previously unexplained developmental delay, it should be considered as a first-tier cytogenetic diagnostic test for children with unexplained developmental delay.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9459-9465
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• 2014

Background: Structural maintenance of chromosomes 4 (SMC-4) is a chromosomal ATPase which plays an important role in regulate chromosome assembly and segregation. However, the role of SMC-4 in the incidence of malignancies, especially colorectal cancer is still poorly understood. Materials and Methods: We here used quantitative PCR and Western blot analysis to examine SMC-4 mRNA and protein levels in primary colorectal cancer and paired normal colonic mucosa. SMC-4 clinicopathological significance was assessed by immunohistochemical staining in a tissue microarray (TMA) in which 118 cases of primary colorectal cancer were paired with noncancerous tissue. The biological function of SMC-4 knockdown was measured by CCK8 and plate colony formation assays. Fluorescence detection has been used to detect cell cycling and apoptosis. Results: SMC-4 expression was significantly higher in colorectal cancer and associated with T stage, N stage, AJCC stage and differentiation. Knockdown of SMC-4 expression significantly suppressed the proliferation of cancer cells and degraded its malignant degree. Conclusions: Our clinical and experimental data suggest that SMC-4 may contribute to the progression of colorectal carcinogenesis. Our study provides a new therapeutic target for colorectal cancer treatment.

• Journal of Genetic Medicine
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• 제8권1호
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• pp.62-66
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• 2011

14q32.33을 포함한 14번 염색체 장완 결실은 드문 질환이다. 14번 염색체의 말단 결실은 여러 임상증상을 공통적으로 보일 수 있으나 결실 절단부 (breakpoint)에 따라 표현형이 다양하게 발생할 수 있다. 저자들은 경련을 동반한 5세 여아에서 array comparative genomic hybridization (array-CGH)와 fluorescence in situ hybridization (FISH) 방법을 이용하여 이전 보고에 비해 가장 작은 14q32.33부위의 0.33 Mb 크기의 말단 결실과 심하지 않은 표현형을 보이는 1례를 경험 하였기에 문헌고찰과 함께 보고하는 바이다.

• Journal of Genetic Medicine
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• 제15권2호
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• pp.64-71
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• 2018

Purpose: Overgrowth syndromes are conditions that involve generalized or localized areas of excess growth. In this study, the clinical, molecular, and genetic characteristics of Korean patients with overgrowth syndrome were analyzed. Materials and Methods: We recruited 13 patients who presented with overgrowth syndrome. All patients fulfilled inclusion criteria of overgrowth syndrome. Analysis of the clinical and molecular investigations of patients with overgrowth syndrome was performed retrospectively. Results: Among the 13 patients with overgrowth syndrome, 9 patients (69.2%) were found to have molecular and genetic causes. Among the seven patients with Sotos syndrome (SS), two had a 5q35microdeletion that was confirmed by fluorescent in situ hybridization. In two patients with SS, intragenic mutations including a novel mutation, c.5993T>A (p.M1998L), were found by Sanger sequencing. One patient had one copy deletion of NDS1 gene which was confirmed by multiplex ligation-dependent probe amplification. Among five patients with Beckwith-Wiedemann syndrome, three had aberrant imprinting control regions; 2 hypermethylation of the differentially methylated region of H19, 1 hypomethylation of the differentially methylated region of Kv. In one patient displaying overlapping clinical features of SS, a de novo heterozygous deletion in the chromosomal region 7q22.1-22.3 was found by single nucleotide polymorphism-based microarray. Conclusion: Considering high detection rate of molecular and genetic abnormalities in this study, rigorous investigations of overgrowth syndrome may be an important tool for the early diagnosis and genetic counseling. A detailed molecular analysis of the rearranged regions may supply the clues for the identification of genes involved in growth regulation.

• 한국콘텐츠학회논문지
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• 제22권2호
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• pp.762-769
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• 2022

산전 진단에서 유전자 검사는 임상 관리 및 부모의 의사 결정에 중요한 정보를 제공하고 있다. 지난 여러 해 동안 G-banidng 핵형 분석, 형광성 제자리 교잡 방법, 염색체 마이크로어레이 및 유전자 패널과 같은 세포유전학적 검사 방법들이 일반적인 산전 진단의 검사의 일부가 되어 발전해 왔다. 그러나 이러한 각각의 방법은 한계를 가지고 있으며 각각의 진단 기술의 단점들을 보완할 수 있는 혁신적인 검사 방법의 도입의 필요성이 매우 필요한 시점이다. 최근 차세대 염기서열 분석에 기반한 유전체 분석 방법의 도입은 현재의 산전 진단에서의 관행에 많은 변화를 주고 있다. 이렇게 산전 진단에서의 유전체 단위의 염기서열 분석은 정교한 해상도와 높은 정확도를 통해 데이터를 빠르게 분석하고 비용을 감소시키는 기술의 혁신을 보여주고 있다. 따라서 본 논문에서는 시퀀싱 기반 산전 진단의 현재 상태와 관련 과제 및 미래 전망에 대하여 검토해 보았다.

• Journal of Genetic Medicine
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• 제19권2호
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• pp.105-110
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• 2022

The microdeletion syndrome of chromosome 2p15p16.1 (MIM: 612513) is an extremely rare contiguous gene deletion syndrome. Microdeletions of varying sizes in the 2p15-16.1 region are associated with developmental delay, intellectual disability, autism spectrum disorder, hypotonia, and craniofacial dysmorphism. Previous studies have identified two critical regions: the proximal 2p15 and distal 2p16.1 regions. BCL11A, PAPOLG, and REL genes play crucial roles in patients with 2p16.1 microdeletion. To our knowledge, only 39 patients have been reported as having 2p15p16.1 microdeletion syndrome. Here, we present another patient with 2p15p16.1 microdeletion syndrome. A nine-month-old boy was referred to our clinic for the psychomotor delay, facial dysmorphism, and congenital hypothyroidism. During his follow-up visits, he was diagnosed with global developmental delay, intellectual disability, abnormal behavior, hypotonia, microcephaly, and abnormal electroencephalography. Using a chromosomal microarray for genetic analysis, a novel, de novo, 622 kb microdeletion of 2p16.1 was identified as one of the critical regions of the 2p15p16.1 microdeletion syndrome. This is the first case of its kind in Korea. We have discussed our case and literature reviews to clarify the relationship between the genes involved and clinical phenotypes in 2p15p16.1 microdeletion syndrome.

• Journal of Genetic Medicine
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• 제19권2호
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• pp.85-93
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• 2022

Purpose: Cornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder caused by genetic variants of the cohesin complex. However, the diverse genetic etiologies and their phenotypic correlations in Korean patients with CdLS are still largely unknown. Hence, this study aimed to clarify the clinical characteristics and genetic background of Korean patients with CdLS. Materials and Methods: The medical records of 15 unrelated patients (3 males and 12 females) genetically confirmed to have CdLS were retrospectively reviewed. All individuals were diagnosed with CdLS using target gene analysis, whole-exome sequencing, and/or chromosomal microarray analysis. The clinical score (CS) was calculated to assess disease severity. Results: The median age at diagnosis was 1.7 (range, 0.0-11.8) years, and median follow-up duration was 3.8 (range, 0.4-11.7) years. Eight (53.3%) patients showed classic phenotypes of CdLS, two (13.3%) showed non-classic phenotypes, and five (33.3%) had other phenotypes sharing limited signs of CdLS. Fifteen causative variants were identified: NIPBL in five (33.3%, including 3 males), SMC1A in three (20.0%), SMC3 in three (20.0%), and HDAC8 in four (26.7%) patients. The CS was significantly higher in the NIPBL group than in the non-NIPBL group (14.2±1.3 vs. 8.7±2.9, P<0.001). Conclusion: We identified the clinical and genetic heterogeneity of CdLS in Korean patients. Patients with variants of NIPBL had a more distinctive phenotype than those carrying variants of other cohesin complex genes (SMC1A, SMC3, and HDAC8). However, further studies are warranted to understand the pathogenesis of CdLS as a cohesinopathy and its genotype-phenotype correlations.

• Journal of Genetic Medicine
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• 제20권1호
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• pp.25-29
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• 2023

The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother. Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.