[논문]A Novel X-Linked Variant of IQSEC2 is Associated with Lennox-Gastaut Syndrome and Mild Intellectual Disability in Three Generations of a Korean Family

Choi, Min-Hyuk; Yang, Jin Ok; Min, Ju-Sik; Lee, Jeong-Ju; Jun, Soo-Young; Lee, Yong-Jae; Yoon, Ji-Yong; Jeon, Su-Jin; Byeon, Iksu; Kang, Joon-Won; Kim, Nam-Soon

doi:10.1089/gtmb.2019.0177

[해외논문] A Novel X-Linked Variant of IQSEC2 is Associated with Lennox-Gastaut Syndrome and Mild Intellectual Disability in Three Generations of a Korean Family

Genetic testing and molecular biomarkers, v.24 no.1, 2020년, pp.54 - 58

Choi, Min-Hyuk (Rare-Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.) , Yang, Jin Ok (Korean BioInformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.) , Min, Ju-Sik (Rare-Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.) , Lee, Jeong-Ju (Rare-Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.) , Jun, Soo-Young (Rare-Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.) , Lee, Yong-Jae (Rare-Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.) , Yoon, Ji-Yong (Rare-Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.) , Jeon, Su-Jin (Rare-Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Repub) , Byeon, Iksu , Kang, Joon-Won , Kim, Nam-Soon

Abstract ▼ AI-Helper

Aim: Lennox-Gastaut syndrome (LGS) is a severe type of childhood-onset epilepsy with multiple types of seizures, specific discharges on electroencephalography, and intellectual disability. However, LGS-related genes are largely unknown. To identify causative genes related to LGS, we collected and analyzed data from a three-generation Korean family in which one member had LGS and two had intellectual disability.Methods: Genomic DNAs were extracted from blood samples of all participants and used in whole-exome sequencing (WES). Genetic variants were detected by the Genome Analysis Toolkit and confirmed by Sanger sequencing. Variant pathogenicity was evaluated by prediction programs and the American College of Medical Genetics criteria. The LGS patient had generalized slow spike-and-wave discharges, multiple types of seizures, and developmental delay.Results: Analyses of the WES data from the family revealed a novel variant (c.1048G>A, p.Ala350Thr) in the IQ motif and Sec7 domain 2 (IQSEC2). This variant is within a highly evolutionarily conserved IQ-like motif, indicating a decrease in the calmodulin-binding capacity or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid transmission. The hemizygous variant in the male with LGS was a maternally inherited X-linked variant from the heterozygous maternal grandmother and mother, both of whom had intellectual disability.Conclusion: These findings indicate that the variant of IQSEC2 triggered both LGS and intellectual disability dependent on sex in this family. We report a novel X-linked inherited IQSEC2 variant for LGS and intellectual disability, which enhances the spectrum of variants in the IQ-like motif of IQSEC2.

Keyword

참고문헌 (26)

Al-Banji, Muradi H., Zahr, Doaa K., Jan, Mohammed M.. Lennox-Gastaut syndrome : Management update. Neurosciences : the official journal of the Pan Arab Union of Neurological Sciences, vol.20, no.3, 207-212.

상세보기
De novo mutations in the classic epileptic encephalopathies. Nature, vol.501, no.7466, 217-221.

상세보기
Asadi-Pooya, A.A., Sharifzade, M.. Lennox-Gastaut syndrome in south Iran: Electro-clinical manifestations. Seizure : European journal of Epilepsy, vol.21, no.10, 760-763.

상세보기
Bendl, Jaroslav, Stourac, Jan, Salanda, Ondrej, Pavelka, Antonin, Wieben, Eric D., Zendulka, Jaroslav, Brezovsky, Jan, Damborsky, Jiri. PredictSNP: Robust and Accurate Consensus Classifier for Prediction of Disease-Related Mutations. PLoS computational biology, vol.10, no.1, e1003440-.

상세보기
Bourgeois, Blaise F. D., Douglass, Laurie M., Sankar, Raman. Lennox‐Gastaut syndrome: A consensus approach to differential diagnosis. Epilepsia : the journal of the International League against Epilepsy, vol.55, no.suppl4, 4-9.

상세보기
Camfield, Peter R.. Definition and natural history of Lennox‐Gastaut syndrome. Epilepsia : the journal of the International League against Epilepsy, vol.52, 3-9.

상세보기
Choi, Yongwook, Chan, Agnes P.. PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics, vol.31, no.16, 2745-2747.

상세보기
Greenberg, D.A., Abreu, P., Hodge, S.E.. The Power to Detect Linkage in Complex Disease by Means of Simple LOD-Score Analyses. American journal of human genetics, vol.63, no.3, 870-879.

상세보기
Kalscheuer, Vera M., James, Victoria M., Himelright, Miranda L., Long, Philip, Oegema, Renske, Jensen, Corinna, Bienek, Melanie, Hu, Hao, Haas, Stefan A., Topf, Maya, Hoogeboom, A. Jeannette M., Harvey, Kirsten, Walikonis, Randall, Harvey, Robert J.. Novel Missense Mutation A789V in IQSEC2 Underlies X-Linked Intellectual Disability in the MRX78 Family. Frontiers in molecular neuroscience, vol.8, 85-.

상세보기
Li, Heng, Durbin, Richard. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics, vol.25, no.14, 1754-1760.

상세보기
McKenna, Aaron, Hanna, Matthew, Banks, Eric, Sivachenko, Andrey, Cibulskis, Kristian, Kernytsky, Andrew, Garimella, Kiran, Altshuler, David, Gabriel, Stacey, Daly, Mark, DePristo, Mark A.. The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome research, vol.20, no.9, 1297-1303.

상세보기
Mignot, Cyril, McMahon, Aoife C., Bar, Claire, Campeau, Philippe M, Davidson, Claire, Buratti, Julien, Nava, Caroline, Jacquemont, Marie-Line, Tallot, Marilyn, Milh, Mathieu, Edery, Patrick, Marzin, Pauline, Barcia, Giulia, Barnerias, Christine, Besmond, Claude, Bienvenu, Thierry, Bruel, Ange-Line, Brunga, Ledia, Ceulemans, Berten, Coubes, Christine, Cristancho, Ana G., Cunningham, Fiona, Dehouck, Marie-Bertille, Donner, Elizabeth J., Duban-Bedu, Bénédicte, Dubourg, Christèle, Gardella, Elena, Gauthier, Julie, Geneviève, David, Gobin-Limballe, Stéphanie, Goldberg, Ethan M., Hagebeuk, Eveline, Hamdan, Fadi F., Hančárová, Miroslava, Hubert, Laurence, Ioos, Christine, Ichikawa, Shoji, Janssens, Sandra, Journel, Hubert, Kaminska, Anna, Keren, Boris, Koopmans, Marije, Lacoste, Caroline, Laššuthová, Petra, Lederer, Damien, Lehalle, Daphné, Marjanovic, Dragan, M&eacu. IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients. Genetics in medicine : official journal of the American College of Medical Genetics, vol.21, no.4, 837-849.

상세보기
Murphy, Jessica A., Jensen, Ole N., Walikonis, Randall S.. BRAG1, a Sec7 domain-containing protein, is a component of the postsynaptic density of excitatory synapses. Brain research, vol.1120, no.1, 35-45.

상세보기
Myers, Kenneth R., Wang, Guangfu, Sheng, Yanghui, Conger, Kathryn K., Casanova, James E., Zhu, J. Julius. Arf6-GEF BRAG1 Regulates JNK-Mediated Synaptic Removal of GluA1-Containing AMPA Receptors: A New Mechanism for Nonsyndromic X-Linked Mental Disorder. The Journal of neuroscience : the official journal of the Society for Neuroscience, vol.32, no.34, 11716-11726.

상세보기
Olson, Heather E., Tambunan, Dimira, LaCoursiere, Christopher, Goldenberg, Marti, Pinsky, Rebecca, Martin, Emilie, Ho, Eugenia, Khwaja, Omar, Kaufmann, Walter E., Poduri, Annapurna. Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome. American Journal of Medical Genetics. Part A, vol.167, no.9, 2017-2025.

상세보기
Redin, Claire, Gérard, Bénédicte, Lauer, Julia, Herenger, Yvan, Muller, Jean, Quartier, Angélique, Masurel-Paulet, Alice, Willems, Marjolaine, Lesca, Gaétan, El-Chehadeh, Salima, Le Gras, Stéphanie, Vicaire, Serge, Philipps, Muriel, Dumas, Michaël, Geoffroy, Véronique, Feger, Claire, Haumesser, Nicolas, Alembik, Yves, Barth, Magalie, Bonneau, Dominique, Colin, Estelle, Dollfus, Hélène, Doray, Bérénice, Delrue, Marie-Ange, Drouin-Garraud, Valérie, Flori, Elisabeth, Fradin, Mélanie, Francannet, Christine, Goldenberg, Alice, Lumbroso, Serge, Mathieu-Dramard, Michèle, Martin-Coignard, Dominique, Lacombe, Didier, Morin, Gilles, Polge, Anne, Sukno, Sylvie, Thauvin-Robinet, Christel, Thevenon, Julien, Doco-Fenzy, Martine, Genevieve, David, Sarda, Pierre, Edery, Patrick, Isidor, Bertrand, Jost, Bernard, Olivier-Faivre, Laurence, Mandel, Jean-Louis . Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. Journal of medical genetics, vol.51, no.11, 724-736.

상세보기
Richards, Sue, Aziz, Nazneen, Bale, Sherri, Bick, David, Das, Soma, Gastier-Foster, Julie, Grody, Wayne W., Hegde, Madhuri, Lyon, Elaine, Spector, Elaine, Voelkerding, Karl, Rehm, Heidi L.. Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in medicine : official journal of the American College of Medical Genetics, vol.17, no.5, 405-424.

상세보기
Rogers, Eli J., Jada, Reem, Schragenheim-Rozales, Kinneret, Sah, Megha, Cortes, Marisol, Florence, Matthew, Levy, Nina S., Moss, Rachel, Walikonis, Randall S., Palty, Raz, Shalgi, Reut, Lichtman, Daniela, Kavushansky, Alexandra, Gerges, Nashaat Z., Kahn, Itamar, Umanah, George K. E., Levy, Andrew P.. An IQSEC2 Mutation Associated With Intellectual Disability and Autism Results in Decreased Surface AMPA Receptors. Frontiers in molecular neuroscience, vol.12, 43-.

상세보기
Sakagami, H., Sanda, M., Fukaya, M., Miyazaki, T., Sukegawa, J., Yanagisawa, T., Suzuki, T., Fukunaga, K., Watanabe, M., Kondo, H.. IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Neuroscience research : the official journal of the Japan Neuroscience Society, vol.60, no.2, 199-212.

상세보기
Schiemann, A. H., Stowell, K. M.. Comparison of pathogenicity prediction tools on missense variants in RYR1 and CACNA1S associated with malignant hyperthermia. British journal of anaesthesia : BJA, vol.117, no.1, 124-128.

상세보기
Shoubridge, Cheryl, Tarpey, Patrick S, Abidi, Fatima, Ramsden, Sarah L, Rujirabanjerd, Sinitdhorn, Murphy, Jessica A, Boyle, Jackie, Shaw, Marie, Gardner, Alison, Proos, Anne, Puusepp, Helen, Raymond, F Lucy, Schwartz, Charles E, Stevenson, Roger E, Turner, Gill, Field, Michael, Walikonis, Randall S, Harvey, Robert J, Hackett, Anna, Futreal, P Andrew, Stratton, Michael R, Gécz, Jozef. Mutations in the guanine nucleotide exchange factor gene IQSEC2 cause nonsyndromic intellectual disability. Nature genetics, vol.42, no.6, 486-488.

상세보기
Tang, Haiming, Thomas, Paul D.. PANTHER-PSEP: predicting disease-causing genetic variants using position-specific evolutionary preservation. Bioinformatics, vol.32, no.14, 2230-2232.

상세보기
Vissers, Lisenka E. L. M., Gilissen, Christian, Veltman, Joris A.. Genetic studies in intellectual disability and related disorders. Nature reviews. Genetics, vol.17, no.1, 9-18.

상세보기
Wang, Kai, Li, Mingyao, Hakonarson, Hakon. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic acids research, vol.38, no.16, e164-e164.

상세보기
Zerem, Ayelet, Haginoya, Kazuhiro, Lev, Dorit, Blumkin, Lubov, Kivity, Sara, Linder, Ilan, Shoubridge, Cheryl, Palmer, Elizabeth Emma, Field, Michael, Boyle, Jackie, Chitayat, David, Gaillard, William D., Kossoff, Eric H., Willems, Marjolaine, Geneviève, David, Tran‐Mau‐Them, Frederic, Epstein, Orna, Heyman, Eli, Dugan, Sarah, Masurel‐Paulet, Alice, Piton, Ame'lie, Kleefstra, Tjitske, Pfundt, Rolph, Sato, Ryo, Tzschach, Andreas, Matsumoto, Naomichi, Saitsu, Hirotomo, Leshinsky‐Silver, Esther, Lerman‐Sagie, Tally. The molecular and phenotypic spectrum of IQSEC2‐related epilepsy. Epilepsia : the journal of the International League against Epilepsy, vol.57, no.11, 1858-1869.

상세보기
Zipper, Rachelle, Baine, Sherri D., Genizi, Jacob, Maoz, Hen, Levy, Nina S., Levy, Andrew P.. Developmental progression of intellectual disability, autism, and epilepsy in a child with an IQSEC 2 gene mutation. Clinical case reports, vol.5, no.10, 1639-1643.

상세보기

LOADING...

활용도 분석정보

상세보기

다운로드

내보내기

활용도 Top5 논문

해당 논문의 주제분야에서 활용도가 높은 상위 5개 콘텐츠를 보여줍니다.
더보기 버튼을 클릭하시면 더 많은 관련자료를 살펴볼 수 있습니다.

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증