• Molecules and Cells
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• 제20권2호
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• pp.228-234
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• 2005

Caenorhabditis elegans him-6 mutants, which show a high incidence of males and partial embryonic lethality, are defective in the orthologue of human Bloom's syndrome protein (BLM). When strain him-6(e1104) containing a missense him-6 mutation was irradiated with ${\gamma}$-rays during germ cell development or embryogenesis, embryonic lethality was higher than in the wild type, suggesting a critical function of the wild type gene in mitotic and pachytene stage germ cells as well as in early embryos. Even in the absence of ${\gamma}$-irradiation, apoptosis was elevated in the germ cells of the him-6 strain and this increase was dependent on a functional p53 homologue (CEP-1), suggesting that spontaneous DNA damage accumulates due to him-6 deficiency. However, induction of germline apoptosis by ionizing radiation was not significantly affected by the deficiency, indicating that HIM-6 has no role in the induction of apoptosis by exogenous DNA damage. We conclude that the C. elegans BLM orthologue is involved in DNA repair in promeiotic cells undergoing homologous recombination, as well as in actively dividing germline and somatic cells.

• Journal of Genetic Medicine
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• 제14권2호
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• pp.56-61
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• 2017

Purpose: Neurofibromatosis type 2 (NF2) is characterized by multiple tumors, including vestibular schwannoma (VS) and others affecting cranial and peripheral nerves. NF2 is caused by mutation of the NF2 gene. The mutation spectrum of NF2 has not been characterized in Korean patients. In the current study, the clinical and genetic characteristics of Korean NF2 patients were analyzed. Materials and Methods: Twenty-five unrelated Korean families were enrolled according to the Manchester criteria. Genetic analysis was performed by direct sequencing and multiplex ligation-dependent probe amplification methods using genomic DNA from peripheral lymphocytes or tumor tissues. Results: All patients had bilateral/unilateral VS and/or other cranial and peripheral nerve tumors. Two patients were familial cases and the other 24 patients were sporadic. Germline NF2 mutations were detected in peripheral lymphocytes from both familial cases, but only in 26.1% of the 23 sporadic families. Somatic mutations were also found in tumor tissues from two of the sporadic families. These somatic mutations were not found in peripheral lymphocytes. A total of 10 different mutations including 2 novel mutations were found in 40.0% of studied families. Five mutations (50.0%) were located in exon 6 of NF2, the FERM domain coding region. Conclusion: Family history was an important factor in identifying germline NF2 mutations. Further study is required to investigate whether exon 6 is a mutation hotspot in Korean NF2 patients and its correlation to phenotypic severity.

• Molecules and Cells
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• 제28권1호
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• pp.43-48
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• 2009

By screening C. elegans mutants for severe defects in germline proliferation, we isolated a new loss-of-function allele of cdc-25.1, bn115. bn115 and another previously identified loss-of-function allele nr2036 do not exhibit noticeable cell division defects in the somatic tissues but have reduced numbers of germ cells and are sterile, indicating that cdc-25.1 functions predominantly in the germ line during postembryonic development, and that cdc-25.1 activity is probably not required in somatic lineages during larval development. We analyzed cell division of germ cells and somatic tissues in bn115 homozygotes with germline-specific anti-PGL-1 immunofluorescence and GFP transgenes that express in intestinal cells, in distal tip cells, and in gonadal sheath cells, respectively. We also analyzed the expression pattern of cdc-25.1 with conventional and quantitative RT-PCR. In the presence of three other family members of cdc-25.1 in C. elegans, defects are observed only in the germ line but not in the somatic tissues in cdc-25.1 single mutants, and cdc-25.1 is expressed predominantly, if not exclusively, in the germ line during postembryonic stages. Our findings indicate that the function of cdc-25.1 is unique in the germ line but likely redundant with other members in the soma.

• Clinical and Experimental Pediatrics
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• 제48권3호
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• pp.337-341
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• 2005

선천성 갑상선 항진증은 드문 질환으로 모체로부터 TSH에 대한 자가항체가 태반을 통해 태아에게 전달되어 생기며 일시적인 경우가 많다. 선천성 갑상선 항진증이 지속되지만 자가면역질환의 검사 소견을 보이지 않을 때에는 TSHR의 돌연변이에 의한 갑상선 항진증을 고려해야 한다. 저자들은 TSHR의 돌연변이에 의한 갑상선 항진증 증례를 2례 경험하였기에 문헌고찰과 함께 보고하는 바이다.

• Radiation Oncology Journal
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• 제26권1호
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• pp.65-73
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• 2008

목적: 40세 이하의 젊은 여성 유방암 환자는 나이 든 여성 보다 BRCA1과 BRCA2 배선돌연변이의 빈도가 상대적으로 높다. 유방암 가족력이 있거나 젊은 나이에 유방암을 진단받은 백인 여성들의 BRCA1/2 돌연변이 암에 대한 연구에서 면역조직화학적으로 BRCA1/2 돌연변이 음성인 암과 다른 특성이 발견되었다. 이 연구의 목적은 유방암 가족력과 관계없이 젊은 나이에 유방암이 발생한 한국 여성을 대상으로 BRCA1/2 돌연변이 유뮤에 따라, 그리고 BRCA1과 BRCA2 각각의 돌연변이에 따라 면역조직화학적 특성으로 상호간의 구별이 가능한지, 면역조직화학적 검사로 BRCA1/2 돌연변이의 가능성을 알아보는 것이 가능한지를 조사하는데 있으며 BRCA와 관련된 암의 예후인자로서의 역할도 분석하였다. 대상 및 방법: BRCA1/2 검사를 시행한 40세 이하의 한국인 젊은 여성 유방암 환자의 유방암 수술 후 병리조직을 찾아서 조직미세배열법으로 슬라이드를 만들었다. 이 검체들의 병리조직, 등급, 림프절 전이, T 병기, 에스트로겐 수용체, 프로게스테론 수용체 및 HER-2 상태와 BRCA1/2의 관계를 비교하였다. 그리고 이 환자들의 BRCA 돌연변이 상태와 면역조직학적, 병리학적 상태와 예후 인자로서의 역할도 조사하였다. 결과: BRCA1/2 돌연변이를 조사한 101명 중 14명에서 16개의 돌연변이가 있었으며(13.9%), 유방암-난소암 가족력이 있는 경우(4/14, 28.6%), 양측성 유방암이 있는 경우(3/9, 33.3%)에 BRCA1/2 돌연변이 빈도가 높았다. 에스트로겐 수용체 음성인 경우 BRCA1/2 양성이 19.4%(12/62)로 에스트로겐 수용체 양성 비율 5.1%(2/37)에 비해 유의하게 높았고(p=0.038), HER-2 음성인 경우 BRCA1/2 돌연변이 음성 비율이 16.5%(13/79)로 양성 비율 4.5%(1/22)에 비해 높은 경향을 보였으며(p=0.073), 프로게스테론 수용체는 차이가 없었다. 에스트로겐 수용체, 프로게스테론 수용체 및 HER-2 모두 음성인 경우(triple negative)는 BRCA1/2 돌연변이 비율이 24.2%(8/33)로 매우 높았다. 종양의 크기, 림프절 전이 상태, HER-2 상태는 단변량 변수와 다변량 변수 모두에서 무병 생존에 유의한 영향을 미치는 인자 이었으나 BRCA1/2 돌연변이 상태는 무병생존에 유의한 인자가 아니었다. 결론: 면역조직화학적으로 에스트로겐 수용체나 HER-2 음성을 보이는 젊은 유방암 환자에서 BRCA1/2 돌연변이 발생이 유의하게 높았으며, 프로게스테론 수용체까지 모두 음성인 경우 BRCA1/2 돌연변이가 있을 확률이 24.2%로 높아서 유방암 유전자 돌연변이 가능성을 예측하는데 도움을 줄 수 있다. 한국인 젊은 여성 유방암 환자에서 BRCA1/2 돌연변이 상태가 무병생존에 유의한 인자는 아니었으나 좀 더 많은 환자와 긴 추적관찰 기간의 추가적인 연구가 필요하다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1917-1923
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• 2016

Background: Lynch Syndrome (LS) is a familial cancer condition caused by germline mutations in DNA mismatch repair genes. Individuals with LS have a greatly increased risk of developing colorectal cancer (CRC) and it is therefore important to identify mutation carriers so they can undergo regular surveillance. Tumor DNA from LS patients characteristically shows microsatellite instability (MSI). Our aim here was to screen young CRC patients for MSI as a first step in the identification of unrecognized cases of LS in the Saudi population. Materials and Methods: Archival tumor tissue was obtained from 284 CRC patients treated at 4 institutes in Dammam and Riyadh between 2006 and 2015 and aged less than 60 years at diagnosis. MSI screening was performed using the BAT-26 microsatellite marker and positive cases confirmed using the pentaplex MSI analysis system. Positive cases were screened for BRAF mutations to exclude sporadic CRC and were evaluated for loss of expression of 4 DNA mismatch repair proteins using immunohistochemistry. Results: MSI was found in 33/284 (11.6%) cases, of which only one showed a BRAF mutation. Saudi MSI cases showed similar instability in the BAT-26 and BAT-25 markers to Australian MSI cases, but significantly lower frequencies of instability in 3 other microsatellite markers. Conclusions: MSI screening of young Saudi CRC patients reveals that approximately 1 in 9 are candidates for LS. Patients with MSI are strongly recommended to undergo genetic counselling and germline mutation testing for LS. Other affected family members can then be identified and offered regular surveillance for early detection of LS-associated cancers.

• Molecules and Cells
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• 제38권3호
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• pp.251-258
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• 2015

Germline mutations in the breast cancer type 2 susceptibility gene (BRCA2) are linked to familial breast cancer and the progressive bone marrow failure syndrome Fanconi anaemia. Established Brca2 mouse knockout models show embryonic lethality, but those with a truncating mutation at the C-terminus survive to birth and develop thymic lymphoma at an early age. To overcome early lethality and investigate the function of BRCA2, we used T cell-specific conditional Brca2 knockout mice, which were previously shown to develop thymic lymphoma at a low penetrance. In the current study we showed that the number of peripheral T cells, particularly na$\ddot{i}$ve pools, drastically declined with age. This decline was primarily ascribed to improper peripheral maintenance. Furthermore, heterozygous mice with one wild-type Brca2 allele manifested reduced T cell numbers, suggesting that Brca2 haploinsufficiency might also result in T cell loss. Our study reveals molecular events occurring in Brca2-deficient T cells and suggests that both heterozygous and homozygous Brca2 mutation may lead to dysfunction in T cell populations.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1683-1686
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• 2012

In the present case control study mRNA expression of the GSTP1 gene, encoding a phase II enzyme that detoxifies via glutathione conjugation, was investigated using semiquantitative PCR followed by SSCP for 49 confirmed head and neck (HN) cancer and 49 control samples. It was found that GSTP1 was upregulated in significantly higher number of cancers (OR 4.2, 95% CI 1.2-15.3). Grade wise correlation was also observed with more up regulation in patients with more advanced grades of HN carcinomas. We also found that 5 patients showed variation in mRNA with a larger product size than expected. Sequencing revealed insertion of an intronic segment between the $6^{th}$ and $7^{th}$ exon of the GSTP1 gene. Germline screening was performed showing mobility shifts which suggested mutation at the DNA level resulting in intronic portion retention. This study is of prime importance for drug design and treatment selection to overcome increased resistance of HN cancers to drugs due to alteration in the GSTP1 gene.

• Journal of Yeungnam Medical Science
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• 제30권2호
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• pp.101-104
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• 2013

Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary disorder caused by a germline mutation of the VHL gene. It is a multi-systemic disorder that is predisposed to benign or malignant tumors of visceral organs such as hemangioblastoma of the central nervous system, renal cell carcinoma, retinal angioma and pheochromocytoma. We report herein a case of VHL disease that initially manifested with aortic valve insufficiency.

• Journal of Genetic Medicine
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• 제15권1호
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• pp.13-16
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• 2018

X-linked juvenile retinoschisis (XLRS) is characterized by the progressive loss of visual acuity and vitreous hemorrhage. XLRS is caused by a mutation of retinoschisin 1 (RS1) gene at Xp22.13. In the current report, a 2-year-old Korean patient with XLRS was described. The germline deletion of exon 1 was identified in the RS1 gene. Considering X-linked inheritance pattern, validation of a carrier state of a patient's mother is important for the genetic counseling of other family members and for the future reproductive plan. To confirm the carrier state of his mother, the multiplex ligation-dependent probe amplification analysis was done using peripheral leukocytes and found the heterozygous deletion of exon 1 in his mother.