138 results on '"Haghighi, Alireza"'
Search Results
2. Distributed interference cancellation in multi-agent scenarios
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Shamsi, Mahdi, Haghighi, Alireza Moslemi, and Marvasti, Farokh
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Computer Science - Multiagent Systems ,Computer Science - Machine Learning ,Computer Science - Robotics ,Electrical Engineering and Systems Science - Signal Processing ,Electrical Engineering and Systems Science - Systems and Control - Abstract
This paper considers the problem of detecting impaired and noisy nodes over network. In a distributed algorithm, lots of processing units are incorporating and communicating with each other to reach a global goal. Due to each one's state in the shared environment, they can help the other nodes or mislead them (due to noise or a deliberate attempt). Previous works mainly focused on proper locating agents and weight assignment based on initial environment state to minimize malfunctioning of noisy nodes. We propose an algorithm to be able to adapt sharing weights according to behavior of the agents. Applying the introduced algorithm to a multi-agent RL scenario and the well-known diffusion LMS demonstrates its capability and generality.
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- 2019
3. Protein-protected metal nanoclusters as diagnostic and therapeutic platforms for biomedical applications
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Zare, Iman, Chevrier, Daniel M., Cifuentes-Rius, Anna, Moradi, Nasrin, Xianyu, Yunlei, Ghosh, Subhadip, Trapiella-Alfonso, Laura, Tian, Ye, Shourangiz-Haghighi, Alireza, Mukherjee, Saptarshi, Fan, Kelong, and Hamblin, Michael R.
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- 2023
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4. An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery
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Haghighi, Alireza, Krier, Joel B, Toth-Petroczy, Agnes, Cassa, Christopher A, Frank, Natasha Y, Carmichael, Nikkola, Fieg, Elizabeth, Bjonnes, Andrew, Mohanty, Anwoy, Briere, Lauren C, Lincoln, Sharyn, Lucia, Stephanie, Gupta, Vandana A, Söylemez, Onuralp, Sutti, Sheila, Kooshesh, Kameron, Qiu, Haiyan, Fay, Christopher J, Perroni, Victoria, Valerius, Jamie, Hanna, Meredith, Frank, Alexander, Ouahed, Jodie, Snapper, Scott B, Pantazi, Angeliki, Chopra, Sameer S, Leshchiner, Ignaty, Stitziel, Nathan O, Feldweg, Anna, Mannstadt, Michael, Loscalzo, Joseph, Sweetser, David A, Liao, Eric, Stoler, Joan M, Nowak, Catherine B, Sanchez-Lara, Pedro A, Klein, Ophir D, Perry, Hazel, Patsopoulos, Nikolaos A, Raychaudhuri, Soumya, Goessling, Wolfram, Green, Robert C, Seidman, Christine E, MacRae, Calum A, Sunyaev, Shamil R, Maas, Richard L, Vuzman, Dana, and Undiagnosed Diseases Network, Brigham and Women’s Hospital FaceBase Project, Brigham Genomic Medicine (BGM)
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Human Genome ,Biotechnology ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Undiagnosed Diseases Network ,Brigham and Women’s Hospital FaceBase Project ,Brigham Genomic Medicine ,Medical biotechnology - Abstract
Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs.
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- 2018
5. A gene-centric strategy for identifying disease-causing rare variants in dilated cardiomyopathy
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Horvat, Claire, Johnson, Renee, Lam, Lien, Munro, Jacob, Mazzarotto, Francesco, Roberts, Angharad M., Herman, Daniel S., Parfenov, Michael, Haghighi, Alireza, McDonough, Barbara, DePalma, Steven R., Keogh, Anne M., Macdonald, Peter S., Hayward, Christopher S., Roberts, Amy, Barton, Paul J. R., Felkin, Leanne E., Giannoulatou, Eleni, Cook, Stuart A., Seidman, J. G., Seidman, Christine E., and Fatkin, Diane
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- 2019
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6. Nemaline myopathy: reclassification of previously reported variants according to ACMG guidelines, and report of novel genetic variants
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Haghighi, Alireza, primary, Alvandi, Zahra, additional, Nilipour, Yalda, additional, Haghighi, Amirreza, additional, Kornreich, Ruth, additional, Nafissi, Shahriar, additional, and Desnick, Robert J., additional
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- 2023
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7. Genetic diagnosis of facioscapulohumeral muscular dystrophy type 1 using rare-variant linkage analysis and long-read genome sequencing
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Li, Kun, Quiat, Daniel, She, Fei, Liu, Yuanwei, He, Rong, Haghighi, Alireza, Liu, Fang, Zhang, Rui, DePalma, Steven Robert, Yang, Ying, Wang, Wen, Seidman, Christine E., Zhang, Ping, and Seidman, Jonathan G.
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- 2024
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8. Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome
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Habeb, Abdelhadi M., Flanagan, Sarah E., Zulali, Mohamed A., Abdullah, Mohamed A., Pomahačová, Renata, Boyadzhiev, Veselin, Colindres, Lesby E., Godoy, Guillermo V., Vasanthi, Thiruvengadam, Al Saif, Ramlah, Setoodeh, Aria, Haghighi, Amirreza, Haghighi, Alireza, Shaalan, Yomna, International Neonatal Diabetes Consortium, Hattersley, Andrew T., Ellard, Sian, and De Franco, Elisa
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- 2018
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9. Copy Number Variation and Structural Genomic Findings in 116 Cases of Sudden Unexplained Death between 1 and 28 Months of Age
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Brownstein, Catherine A., primary, Douard, Elise, additional, Haynes, Robin L., additional, Koh, Hyun Yong, additional, Haghighi, Alireza, additional, Keywan, Christine, additional, Martin, Bree, additional, Alexandrescu, Sanda, additional, Haas, Elisabeth A., additional, Vargas, Sara O., additional, Wojcik, Monica H., additional, Jacquemont, Sébastien, additional, Poduri, Annapurna H., additional, Goldstein, Richard D., additional, and Holm, Ingrid A., additional
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- 2022
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10. Ribosomal protein S6 kinase beta-1 gene variants cause hypertrophic cardiomyopathy
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Pratul Kumar Jain, Shashank Jayappa, Thiagarajan Sairam, Anupam Mittal, Sayan Paul, Vinay J Rao, Harshil Chittora, Deepak K Kashyap, Dasaradhi Palakodeti, Kumarasamy Thangaraj, Jayaprakash Shenthar, Rakesh Koranchery, Ranjith Rajendran, Haghighi Alireza, Kurukkanparampil Sreedharan Mohanan, Andiappan Rathinavel, and Perundurai S Dhandapany
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Heterozygote ,Ribosomal Protein S6 Kinases ,Mutation ,Genetics ,Humans ,Ribosomal Protein S6 Kinases, 70-kDa ,Exome ,Cardiomyopathy, Hypertrophic ,Cardiomyopathies ,Genetics (clinical) - Abstract
BackgroundHypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease with preserved or increased ejection fraction in the absence of secondary causes. Mutations in the sarcomeric protein-encoding genes predominantly cause HCM. However, relatively little is known about the genetic impact of signalling proteins on HCM.Methods and resultsHere, using exome and targeted sequencing methods, we analysed two independent cohorts comprising 401 Indian patients with HCM and 3521 Indian controls. We identified novel variants in ribosomal protein S6 kinase beta-1 (RPS6KB1 or S6K1) gene in two unrelated Indian families as a potential candidate gene for HCM. The two unrelated HCM families had the same heterozygous missense S6K1 variant (p.G47W). In a replication association study, we identified two S6K1 heterozygotes variants (p.Q49K and p.Y62H) in the UK Biobank cardiomyopathy cohort (n=190) compared with matched controls (n=16 479). These variants are neither detected in region-specific controls nor in the human population genome data. Additionally, we observed an S6K1 variant (p.P445S) in an Arab patient with HCM. Functional consequences were evaluated using representative S6K1 mutated proteins compared with wild type in cellular models. The mutated proteins activated the S6K1 and hyperphosphorylated the rpS6 and ERK1/2 signalling cascades, suggesting a gain-of-function effect.ConclusionsOur study demonstrates for the first time that the variants in the S6K1 gene are associated with HCM, and early detection of the S6K1 variant carriers can help to identify family members at risk and subsequent preventive measures. Further screening in patients with HCM with different ethnic populations will establish the specificity and frequency of S6K1 gene variants.
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- 2021
11. Gold nanostructures : synthesis, properties, and neurological applications
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Zare, Iman, Yaraki, Mohammad Tavakkoli, Speranza, Giorgio, Najafabadi, Alireza Hassani, Haghighi, Alireza Shourangiz, Nik, Amirala Bakhshian, Manshian, Bella B., Saraiva, Claudia, Soenen, Stefaan J., Kogan, Marcelo J., Lee, Jee Woong, Apollo, Nicholas V., Bernardino, Liliana, Araya, Eyleen, Mayer, Dirk, Mao, Guangzhao, Hamblin, Michael R., Zare, Iman, Yaraki, Mohammad Tavakkoli, Speranza, Giorgio, Najafabadi, Alireza Hassani, Haghighi, Alireza Shourangiz, Nik, Amirala Bakhshian, Manshian, Bella B., Saraiva, Claudia, Soenen, Stefaan J., Kogan, Marcelo J., Lee, Jee Woong, Apollo, Nicholas V., Bernardino, Liliana, Araya, Eyleen, Mayer, Dirk, Mao, Guangzhao, and Hamblin, Michael R.
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Recent advances in technology are expected to increase our current understanding of neuroscience. Nanotechnology and nanomaterials can alter and control neural functionality in both in vitro and in vivo experimental setups. The intersection between neuroscience and nanoscience may generate long-term neural interfaces adapted at the molecular level. Owing to their intrinsic physicochemical characteristics, gold nanostructures (GNSs) have received much attention in neuroscience, especially for combined diagnostic and therapeutic (theragnostic) purposes. GNSs have been successfully employed to stimulate and monitor neurophysiological signals. Hence, GNSs could provide a promising solution for the regeneration and recovery of neural tissue, novel neuroprotective strategies, and integrated implantable materials. This review covers the broad range of neurological applications of GNS-based materials to improve clinical diagnosis and therapy. Sub-topics include neurotoxicity, targeted delivery of therapeutics to the central nervous system (CNS), neurochemical sensing, neuromodulation, neuroimaging, neurotherapy, tissue engineering, and neural regeneration. It focuses on core concepts of GNSs in neurology, to circumvent the limitations and significant obstacles of innovative approaches in neurobiology and neurochemistry, including theragnostics. We will discuss recent advances in the use of GNSs to overcome current bottlenecks and tackle technical and conceptual challenges.
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- 2022
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12. Copy Number Variation and Structural Genomic Findings in 116 Cases of Sudden Unexplained Death between 1 and 28 Months of Age.
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Brownstein, Catherine A., Douard, Elise, Haynes, Robin L., Koh, Hyun Yong, Haghighi, Alireza, Keywan, Christine, Martin, Bree, Alexandrescu, Sanda, Haas, Elisabeth A., Vargas, Sara O., Wojcik, Monica H., Jacquemont, Sébastien, Poduri, Annapurna H., Goldstein, Richard D., and Holm, Ingrid A.
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- 2023
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13. Genetic Determinants of Sudden Unexpected Death in Pediatrics
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Koh, Hyun Yong, primary, Haghighi, Alireza, additional, Keywan, Christine, additional, Alexandrescu, Sanda, additional, Plews-Ogan, Erin, additional, Haas, Elisabeth A., additional, Brownstein, Catherine A., additional, Vargas, Sara O., additional, Haynes, Robin L., additional, Berry, Gerard T., additional, Holm, Ingrid A., additional, Poduri, Annapurna H., additional, and Goldstein, Richard D., additional
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- 2022
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14. The "Velvet Revolution" of Iranian Puritan Hardliners: Mahmoud Ahmadinejad's Rise to Power
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Haghighi, Alireza N. and Tahmasebi, Victoria
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- 2006
15. Contribution of Noncanonical Splice Variants toTTNTruncating Variant Cardiomyopathy
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Patel, Parth N., primary, Ito, Kaoru, additional, Willcox, Jon A.L., additional, Haghighi, Alireza, additional, Jang, Min Young, additional, Gorham, Joshua M., additional, DePalma, Steven R., additional, Lam, Lien, additional, McDonough, Barbara, additional, Johnson, Renee, additional, Lakdawala, Neal K., additional, Roberts, Amy, additional, Barton, Paul J.R., additional, Cook, Stuart A., additional, Fatkin, Diane, additional, Seidman, Christine E., additional, and Seidman, J.G., additional
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- 2021
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16. Genetic and Phenotypic Landscape of Peripartum Cardiomyopathy
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Goli, Rahul, Li, Jian, Brandimarto, Jeff, Levine, Lisa D., Riis, Valerie, McAfee, Quentin, Depalma, Steven, Haghighi, Alireza, Seidman, J. G., Seidman, Christine E., Jacoby, Daniel, Macones, George, Judge, Daniel P., Rana, Sarosh, Margulies, Kenneth B., Cappola, Thomas P., Alharethi, Rami, Damp, Julie, Hsich, Eileen, Elkayam, Uri, Sheppard, Richard, Alexis, Jeffrey D., Boehmer, John, Kamiya, Chizuko, Gustafsson, Finn, Damm, Peter, Ersbøll, Anne S., Goland, Sorel, Hilfiker-Kleiner, Denise, McNamara, Dennis M., Arany, Zolt, Goli, Rahul, Li, Jian, Brandimarto, Jeff, Levine, Lisa D., Riis, Valerie, McAfee, Quentin, Depalma, Steven, Haghighi, Alireza, Seidman, J. G., Seidman, Christine E., Jacoby, Daniel, Macones, George, Judge, Daniel P., Rana, Sarosh, Margulies, Kenneth B., Cappola, Thomas P., Alharethi, Rami, Damp, Julie, Hsich, Eileen, Elkayam, Uri, Sheppard, Richard, Alexis, Jeffrey D., Boehmer, John, Kamiya, Chizuko, Gustafsson, Finn, Damm, Peter, Ersbøll, Anne S., Goland, Sorel, Hilfiker-Kleiner, Denise, McNamara, Dennis M., and Arany, Zolt
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Background: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM. Methods: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN, and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated. Results: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [P∗]=1.2×10-46). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P∗=7.0×10-8), DSP (odds ratio=14.9, P∗=1.0×10-8), and BAG3 (odds ratio=53.1, P∗=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P=2.5×10-4), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery. Conclusions: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genet
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- 2021
17. Mechanisms of Congenital Heart Disease Caused by NAA15 Haploinsufficiency
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Ward, Tarsha, primary, Tai, Warren, additional, Morton, Sarah, additional, Impens, Francis, additional, Van Damme, Petra, additional, Van Haver, Delphi, additional, Timmerman, Evy, additional, Venturini, Gabriela, additional, Zhang, Kehan, additional, Jang, Min Young, additional, Willcox, Jon A.L., additional, Haghighi, Alireza, additional, Gelb, Bruce D., additional, Chung, Wendy K., additional, Goldmuntz, Elizabeth, additional, Porter, George A., additional, Lifton, Richard P., additional, Brueckner, Martina, additional, Yost, H. Joseph, additional, Bruneau, Benoit G., additional, Gorham, Joshua, additional, Kim, Yuri, additional, Pereira, Alexandre, additional, Homsy, Jason, additional, Benson, Craig C., additional, DePalma, Steven R., additional, Varland, Sylvia, additional, Chen, Christopher S., additional, Arnesen, Thomas, additional, Gevaert, Kris, additional, Seidman, Christine, additional, and Seidman, J.G., additional
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- 2021
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18. Association of Parental Consanguinity With Papillary Thyroid Carcinoma: A Case-Control Study
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Zayed, Ayman A, primary, Amarin, Justin Z, additional, Al-Ani, Abdallah T, additional, Altell, Tareq L, additional, Abdelhamid, Sultan S, additional, Qirem, Murad M, additional, Fahmawi, Suhib M, additional, Elshebli, Sanad M, additional, Hamo, Khair M, additional, Zaghlol, Louay Y, additional, Tierney, Michael E, additional, Zayed, Jana A, additional, and Haghighi, Alireza, additional
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- 2021
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19. SEQUENCE VARIANTS IN TITIN CAUSING SPLICING DEFECTS AND CARDIOMYOPATHY: INSIGHTS FOR GENE BASED DIAGNOSIS AND NORMAL PHYSIOLOGY
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Patel, Parth, primary, Ito, Kaoru, additional, Willcox, Jon A.L., additional, Gorham, Joshua M., additional, DePalma, Steven, additional, Lam, Lien, additional, Haghighi, Alireza, additional, Sharma, Arun, additional, McDonough, Barbara, additional, Johnson, Renee, additional, Fatkin, Diane, additional, Seidman, Christine, additional, and Seidman, Jonathan, additional
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- 2020
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20. Genetic parameters and combining ability of some important traits in rice (Oryza sativa L.)
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Ezatollah Farshadfar, Mehrzad Allahgholipour, and Hasanalideh Haghighi Alireza
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lcsh:Genetics ,Oryza sativa ,lcsh:QH426-470 ,rice ,F2 progenies ,Botany ,diallel analysis ,genetic parameters ,Genetics ,Plant Science ,Biology ,combining ability - Abstract
In order to study the combining ability, genetic parameters and gene actions of yield, yield components and quality characters in rice, fifteen F2 generation of a 6?6 diallel cross, excluding reciprocals, was grown in a randomized complete block design (RCBD) with three replications. The results of analysis of variance showed significant differences between the genotypes for grain yield (GY), 100-grain weight (HGW), number of panicles per plant (PN), panicle length (PL), number of full grains per panicle (FGN) and for quality characters including amylose content (AC) and gel consistency (GC). The results of combining ability analysis revealed that general combining ability (GCA) and specific combining ability (SCA) were significant for characters GY, FGN, GC, AC, HGW and PN indicating the involvement of additive and non-additive effects in their inheritance, however high amounts of Bakers ratio remarked that additive gene effect had more portion in controlling these traits. The best combiners for GY, HGW, FGN, PN and PL, were RI18447-2, IR 50, Daylamani, RI18430-46 and Daylamani respectively. For AC and GC, the best combiner was Daylamani. Hayman's graphs showed that regression line passed below the origin cutting Wr axis in the negative region for HGW, PN, PL and GC, indicating the presence of over dominance. Estimates of genetic parameters showed significant amount of H1 and H2, and non-significant amount of D for the characters GY, PN, PL and GC, which confirmed the existence of dominance in the inheritance of these traits.
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- 2017
21. The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease
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Ng, Yi Shiau, Alston, Charlotte L., Diodato, Daria, Morris, Andrew A., Ulrick, Nicole, Kmoch, Stanislav, Houstek, Josef, Martinelli, Diego, Haghighi, Alireza, Atiq, Mehnaz, Gamero, Montserrat Anton, Garcia-Martinez, Elena, Kratochvilova, Hana, Santra, Saikat, Brown, Ruth M., Brown, Garry K., Ragge, Nicola, Monavari, Ahmad, Pysden, Karen, Ravn, Kirstine, Casey, Jillian P., Khan, Arif, Chakrapani, Anupam, Vassallo, Grace, Simons, Cas, McKeever, Karl, O'Sullivan, Siobhan, Childs, Anne-Marie, Ostergaard, Elsebet, Vanderver, Adeline, Goldstein, Amy, Vogt, Julie, Taylor, Robert W., McFarland, Robert, [Ng, Yi Shiau] Newcastle Univ, Inst Neurosci, Wellcome Trust Ctr Mitochondrial Res, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England, [Alston, Charlotte L.] Newcastle Univ, Inst Neurosci, Wellcome Trust Ctr Mitochondrial Res, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England, [Taylor, Robert W.] Newcastle Univ, Inst Neurosci, Wellcome Trust Ctr Mitochondrial Res, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England, [McFarland, Robert] Newcastle Univ, Inst Neurosci, Wellcome Trust Ctr Mitochondrial Res, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England, [Diodato, Daria] Children Res Hosp Bambino Gesu, Neuromuscular & Neurodegenerat Dis Unit, Rome, Italy, [Morris, Andrew A.] Cent Manchester Univ Hosp NHS Fdn Trust, St Marys Hosp, Dept Med Genet, Manchester, Lancs, England, [Ulrick, Nicole] George Washington Univ, Sch Med, Childrens Natl Hlth Syst, Dept Neurol, Washington, DC USA, [Vanderver, Adeline] George Washington Univ, Sch Med, Childrens Natl Hlth Syst, Dept Neurol, Washington, DC USA, [Kmoch, Stanislav] Charles Univ Prague, Inst Inherited Metab Disorders, Fac Med 1, Prague, Czech Republic, [Houstek, Josef] Acad Sci Czech Republic, Inst Physiol, Prague, Czech Republic, [Martinelli, Diego] Children Res Hosp Bambino Gesu, Div Metab, Rome, Italy, [Haghighi, Alireza] Harvard Med Sch, Dept Genet, Boston, MA USA, [Haghighi, Alireza] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA, [Haghighi, Alireza] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA, [Atiq, Mehnaz] Aga Khan Univ, Dept Pediat, Karachi, Pakistan, [Gamero, Montserrat Anton] Hosp Univ Reina Sofia, Pediat Nephrol Unit, Cordoba, Spain, [Garcia-Martinez, Elena] Hosp Univ Reina Sofia, Pediat Nephrol Unit, Cordoba, Spain, [Kratochvilova, Hana] Charles Univ Prague, Fac Med 1, Dept Pediat & Adolescent Med, Prague, Czech Republic, [Kratochvilova, Hana] Gen Univ Hosp Prague, Prague, Czech Republic, [Santra, Saikat] Birmingham Childrens Hosp NHS Fdn Trust, Dept Clin Inherited Metab Disorders, Birmingham, W Midlands, England, [Brown, Ruth M.] Oxford Univ Hosp NHS Fdn Trust, Churchill Hosp, Oxford Med Genet Labs, Oxford, England, [Brown, Garry K.] Oxford Univ Hosp NHS Fdn Trust, Churchill Hosp, Oxford Med Genet Labs, Oxford, England, [Ragge, Nicola] Birmingham Womens NHS Fdn Trust, West Midlands Reg Genet Serv, Clin Genet Unit, Birmingham, W Midlands, England, [Monavari, Ahmad] Temple St Childrens Univ Hosp, Natl Ctr Inherited Metab Disorders, Dublin, Ireland, [Pysden, Karen] Leeds Gen Infirm, Dept Paediat Med, Leeds, W Yorkshire, England, [Childs, Anne-Marie] Leeds Gen Infirm, Dept Paediat Med, Leeds, W Yorkshire, England, [Ravn, Kirstine] Rigshosp, Copenhagen Univ Hosp, Dept Clin Genet, Copenhagen, Denmark, [Ostergaard, Elsebet] Rigshosp, Copenhagen Univ Hosp, Dept Clin Genet, Copenhagen, Denmark, [Casey, Jillian P.] Temple St Childrens Univ Hosp, Dept Clin Genet, Dublin, Ireland, [Khan, Arif] Leicester Royal Infirm, Leicester Childrens Hosp, Leicester, Leics, England, [Chakrapani, Anupam] Great Ormond St Hosp NHS Fdn Trust, Dept Metab Med, London, England, [Vassallo, Grace] Cent Manchester Univ Hosp NHS Fdn Trust, Dept Paediat Neurol, Manchester, Lancs, England, [Simons, Cas] Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia, [McKeever, Karl] Royal Belfast Hosp Sick Children, Dept Paediat Med, Belfast, Antrim, North Ireland, [O'Sullivan, Siobhan] Royal Belfast Hosp Sick Children, Dept Paediat Med, Belfast, Antrim, North Ireland, [Goldstein, Amy] Childrens Hosp Pittsburgh, Div Child Neurol, Pittsburgh, PA USA, [Vogt, Julie] Univ Birmingham, Sch Clin & Expt Med, Ctr Rare Dis & Personalised Med, Dept Med & Mol Genet, Birmingham, W Midlands, England, [Ragge, Nicola] Oxford Brookes Univ, Fac Hlth & Life Sci, Oxford, England, Wellcome Trust, Medical Research Council, UK NHS Specialised Services and Newcastle upon Tyne Hospitals NHS Foundation Trust, National Institute for Health Research (NIHR), Charles University, BIOCEV -Biotechnology and Biomedicine Centre of the Academy of Sciences, European Regional Development Fund, Grant Agency of the Czech Republic, Ministry of Education of the Czech Republic, Ministry of Education, Ministry of Health of the Czech Republic, MRC, National Institute for Health Research, and NIHR Newcastle Biomedical Research Centre
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Translation ,Complex deficiencies ,Rmnd1 mutation ,Defect ,Renal-failure ,Encephaloneuromyopathy - Abstract
Background Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects. Methods We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype–phenotype correlates and performed survival analysis to identify prognostic factors. Results We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, p.(Leu435Phe); c.830+1G>A and c.1317+1G>T. Together with all previously published cases (n=32), we show that congenital sensorineural deafness, hypotonia, developmental delay and lactic acidaemia are common clinical manifestations with disease onset under 2 years. Renal involvement is more prevalent than seizures (66% vs 44%). In addition, median survival time was longer in patients with renal involvement compared with those without renal disease (6 years vs 8 months, p=0.009). The neurological phenotype also appears milder in patients with renal involvement. Conclusions The clinical phenotypes and prognosis associated with RMND1 mutations are more heterogeneous than that were initially described. Regular monitoring of kidney function is imperative in the clinical practice in light of nephropathy being present in over 60% of cases. Furthermore, renal replacement therapy should be considered particularly in those patients with mild neurological manifestation as shown in our study that four recipients of kidney transplant demonstrate good clinical outcome to date.
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- 2016
22. Erratum. Recessively Inherited LRBA Mutations Cause Autoimmunity Presenting as Neonatal Diabetes. Diabetes 2017;66:2316–2322
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Johnson, Matthew B., primary, De Franco, Elisa, additional, Lango Allen, Hana, additional, Al Senani, Aisha, additional, Elbarbary, Nancy, additional, Siklar, Zeynep, additional, Berberoglu, Merih, additional, Imane, Zineb, additional, Haghighi, Alireza, additional, Razavi, Zahra, additional, Ullah, Irfan, additional, Alyaarubi, Saif, additional, Gardner, Daphne, additional, Ellard, Sian, additional, Hattersley, Andrew T., additional, and Flanagan, Sarah E., additional
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- 2018
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23. Recessively Inherited LRBA Mutations Cause Autoimmunity Presenting as Neonatal Diabetes
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Johnson, Matthew B., primary, De Franco, Elisa, additional, Lango Allen, Hana, additional, Al Senani, Aisha, additional, Elbarbary, Nancy, additional, Siklar, Zeynep, additional, Berberoglu, Merih, additional, Imane, Zineb, additional, Haghighi, Alireza, additional, Razavi, Zahra, additional, Ullah, Irfan, additional, Alyaarubi, Saif, additional, Gardner, Daphne, additional, Güven, Ayla, additional, Ellard, Sian, additional, Hattersley, Andrew T., additional, and Flanagan, Sarah E., additional
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- 2017
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24. Characterization of CSF2RA mutation related juvenile pulmonary alveolar proteinosis
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Hildebrandt, Jenna, Yalcin, Ebru, Bresser, Hans-Georg, Cinel, Guzin, Gappa, Monika, Haghighi, Alireza, Kiper, Nural, Khalilzadeh, Soheila, Reiter, Karl, Sayer, John, Schwerk, Nicolaus, Sibbersen, Anke, Van daele, Sabine, Nübling, Georg, Lohse, Peter, Griese, Matthias, and Çocuk Sağlığı ve Hastalıkları
- Subjects
EXPRESSION ,Medicine(all) ,Male ,Adolescent ,Genotype ,DELETION ,Research ,Infant ,PHENOTYPES ,CHILDREN ,Pulmonary Alveolar Proteinosis ,GENE ,CLASSIFICATION ,Young Adult ,Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ,Child, Preschool ,Mutation ,Medicine and Health Sciences ,Leukocytes, Mononuclear ,Humans ,Genetics(clinical) ,Pharmacology (medical) ,Female ,Child ,DIFFUSE LUNG-DISEASE - Abstract
Background Juvenile pulmonary alveolar proteinosis (PAP) due to CSF2RA mutations is a rare disorder with only a few cases described worldwide. Methods We identified nine children with severe diffuse interstitial lung disease due to CSF2RA mutations. Clinical course, diagnostic findings and treatment were evaluated and correlated to the genotype. Functional impairment of the intracellular JAK/pStat5 signaling pathway was assessed using flow-cytometry of peripheral mononuclear cells (PBMC) and granulocytes. Results We identified six individuals with homozygous missense/nonsense/frameshift mutations and three individuals homozygous for a deletion of the complete CSF2RA gene locus. Overall, four novel mutations (c.1125 + 1G > A, duplication exon 8, deletion exons 2–13, Xp22.3/Yp11.3) were found. Reduced STAT5 phosphorylation in PBMC and granulocytes was seen in all cases examined (n = 6). Pulmonary symptoms varied from respiratory distress to clinically silent. Early disease onset was associated with a more severe clinical phenotype (p = 0.0092). No association was seen between severity of phenotype at presentation and future clinical course or extent of genetic damage. The clinical course was favorable in all subjects undergoing whole lung lavage (WLL) treatment. Conclusions Our cohort broadens the spectrum of knowledge about the clinical variability and genotype-phenotype correlations of juvenile PAP, and illustrates the favorable outcome of WLL treatment in severely affected patients. Electronic supplementary material The online version of this article (doi:10.1186/s13023-014-0171-z) contains supplementary material, which is available to authorized users.
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- 2014
25. The clinical, biochemical and genetic features associated withRMND1-related mitochondrial disease
- Author
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Ng, Yi Shiau, primary, Alston, Charlotte L, additional, Diodato, Daria, additional, Morris, Andrew A, additional, Ulrick, Nicole, additional, Kmoch, Stanislav, additional, Houštěk, Josef, additional, Martinelli, Diego, additional, Haghighi, Alireza, additional, Atiq, Mehnaz, additional, Gamero, Montserrat Anton, additional, Garcia-Martinez, Elena, additional, Kratochvílová, Hana, additional, Santra, Saikat, additional, Brown, Ruth M, additional, Brown, Garry K, additional, Ragge, Nicola, additional, Monavari, Ahmad, additional, Pysden, Karen, additional, Ravn, Kirstine, additional, Casey, Jillian P, additional, Khan, Arif, additional, Chakrapani, Anupam, additional, Vassallo, Grace, additional, Simons, Cas, additional, McKeever, Karl, additional, O'Sullivan, Siobhan, additional, Childs, Anne-Marie, additional, Østergaard, Elsebet, additional, Vanderver, Adeline, additional, Goldstein, Amy, additional, Vogt, Julie, additional, Taylor, Robert W, additional, and McFarland, Robert, additional
- Published
- 2016
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- View/download PDF
26. PEDIATRIC CARDIOMYOPATHY MUTATIONS IN A HIGHLY CONSANGUINEOUS POPULATION
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Fahed, Akl C., primary, Candan, Şükrü, additional, Haghighi, Alireza, additional, DePalma, Steven, additional, McDonough, Barbara, additional, Erer, Betül, additional, Ekmekçi, Ahmet, additional, Bornaun, Helen, additional, Öztarhan, Kazum, additional, Aydin, Hatip, additional, Seidman, Jonathan, additional, and Seidman, Christine, additional
- Published
- 2016
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- View/download PDF
27. Identification of a novel nonsense mutation and a missense substitution in the AGPAT2 gene causing congenital generalized lipodystrophy type 1
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Haghighi, Amirreza, Razzaghy-Azar, Maryam, Talea, Ali, Sadeghian, Mahnaz, Ellard, Sian, and Haghighi, Alireza
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- 2012
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28. TRANS, A study of motion and geometry
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Borhani Haghighi, Alireza, Architecture, Dunay, Robert J., Galloway, William U., Thompson, Steven R., and Schubert, Robert P.
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Motion ,LD5655.V855 2012.H344 ,Geometry - Abstract
A building can be conceptualized in terms of its geometry and force. Between the two concepts of Motion and Rest, architecture mostly tends towards the idea of Rest. However, mechanical form is based on the idea of Motion. Mechanics is often referred to as the geometry of motion and describes the motion of objects with consideration of force and geometry; common domains between architecture and mechanics. The way that mechanical engineers integrate motion into geometry and force can encourage architects to incorporate geometry in an unconventional method. In architecture and mechanics, most movements have a practical purpose, but movements become poetic when they go beyond the purely practical. The poetry of a movement is not automatically a by-product of its functional or economic optimization. This book is concerned with such moving parts. Master of Architecture
- Published
- 2012
29. Missense mutation outside the forkhead domain of FOXL2 causes a severe form of BPES type II
- Author
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Haghighi, Alireza, Verdin, Hannah, Haghighi-Kakhki, Hamidreza, Piri, Niloofar, Gohari, Nasrollah Saleh, and De Baere, Elfride
- Subjects
Forkhead Box Protein L2 ,Male ,Heterozygote ,Genotype ,Genetic Linkage ,PTOSIS ,DNA Mutational Analysis ,Molecular Sequence Data ,GENOTYPE-PHENOTYPE CORRELATION ,Mutation, Missense ,Blepharophimosis ,Iran ,Severity of Illness Index ,DISEASE ,BLEPHAROPHIMOSIS ,Humans ,Genes, Dominant ,TRANSCRIPTION FACTOR FOXL2 ,Base Sequence ,Biology and Life Sciences ,TIME QUANTITATIVE PCR ,Forkhead Transcription Factors ,TRANSACTIVATION ,Pedigree ,Protein Structure, Tertiary ,Phenotype ,EPICANTHUS INVERSUS SYNDROME ,Skin Abnormalities ,Female ,Research Article - Abstract
Purpose: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a developmental disease characterized by a complex eyelid malformation associated or not with premature ovarian failure (POF). BPES is essentially an autosomal dominant disease, due to mutations in the forkhead box L2 (FOXL2) gene, encoding a forkhead transcription factor. More than one hundred unique FOXL2 mutations have been described in BPES in different populations, many of which are missense mutations in the forkhead domain. Here, we report on a very severe form of BPES resulting from a missense mutation outside the forkhead domain. Methods: A clinical and molecular genetic investigation was performed in affected and unaffected members of an Iranian family with BPES. The FOXL2 coding region was sequenced in an index case. Targeted mutation testing was performed in 8 family members. Results: We have identified a heterozygous FOXL2 missense mutation c.650C -> G (p.Ser217Cys) co-segregating with disease in members of a three-generation family with BPES type II. Only few missense mutations have been reported outside the forkhead domain so far. They were all found in mild BPES, in line with in vitro studies demonstrating mostly normal localization and normal or increased transactivation properties of the mutant proteins. Unlike previous studies, affected members of the family studied here showed a severe BPES phenotype, with bilateral amblyopia due to uncorrected ptosis. Conclusions: This is the first study demonstrating a severe BPES phenotype resulting from a FOXL2 missense mutation outside the forkhead domain, expanding our knowledge about the phenotypic consequences of missense mutations outside the forkhead domain in BPES.
- Published
- 2012
30. Genetics of GNE myopathy in the non-Jewish Persian population
- Author
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Haghighi, Alireza, primary, Nafissi, Shahriar, additional, Qurashi, Abrar, additional, Tan, Zheng, additional, Shamshiri, Hosein, additional, Nilipour, Yalda, additional, Haghighi, Amirreza, additional, Desnick, Robert J, additional, and Kornreich, Ruth, additional
- Published
- 2015
- Full Text
- View/download PDF
31. Homozygosity Mapping and Whole Exome Sequencing Reveal a Novel Homozygous COL18A1 Mutation Causing Knobloch Syndrome
- Author
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Haghighi, Alireza, Tiwari, Amit, Piri, Niloofar, Nuernberg, Gudrun, Saleh-Gohari, Nasrollah, Haghighi, Amirreza, Neidhardt, John, Nuernberg, Peter, Berger, Wolfgang, Haghighi, Alireza, Tiwari, Amit, Piri, Niloofar, Nuernberg, Gudrun, Saleh-Gohari, Nasrollah, Haghighi, Amirreza, Neidhardt, John, Nuernberg, Peter, and Berger, Wolfgang
- Abstract
The aim of this study was to identify the genetic basis of a chorioretinal dystrophy with high myopia of unknown origin in a child of a consanguineous marriage. The proband and ten family members of Iranian ancestry participated in this study. Linkage analysis was carried out with DNA samples of the proband and her parents by using the Human SNP Array 6.0. Whole exome sequencing (WES) was performed with the patients' DNA. Specific sequence alterations within the homozygous regions identified by whole exome sequencing were verified by Sanger sequencing. Upon genetic analysis, a novel homozygous frameshift mutation was found in exon 42 of the COL18A1 gene in the patient. Both parents were heterozygous for this sequence variation. Mutations in COL18A1 are known to cause Knobloch syndrome (KS). Retrospective analysis of clinical records of the patient revealed surgical removal of a meningocele present at birth. The clinical features shown by our patient were typical of KS with the exception of chorioretinal degeneration which is a rare manifestation. This is the first case of KS reported in a family of Iranian ancestry. We identified a novel disease-causing (deletion) mutation in the COL18A1 gene leading to a frameshift and premature stop codon in the last exon. The mutation was not present in SNP databases and was also not found in 192 control individuals. Its localization within the endostatin domain implicates a functional relevance of endostatin in KS. A combined approach of linkage analysis and WES led to a rapid identification of the disease-causing mutation even though the clinical description was not completely clear at the beginning.
- Published
- 2014
32. Homozygosity Mapping and Whole Exome Sequencing Reveal a Novel Homozygous COL18A1 Mutation Causing Knobloch Syndrome
- Author
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Haghighi, Alireza, primary, Tiwari, Amit, additional, Piri, Niloofar, additional, Nürnberg, Gudrun, additional, Saleh-Gohari, Nasrollah, additional, Haghighi, Amirreza, additional, Neidhardt, John, additional, Nürnberg, Peter, additional, and Berger, Wolfgang, additional
- Published
- 2014
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33. Recessively Inherited Mutations Cause Autoimmunity Presenting as Neonatal Diabetes.
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Johnson, Matthew B., De Franco, Elisa, Lango Allen, Hana, Al Senani, Aisha, Elbarbary, Nancy, Siklar, Zeynep, Berberoglu, Merih, Imane, Zineb, Haghighi, Alireza, Razavi, Zahra, Ullah, Irfan, Alyaarubi, Saif, Gardner, Daphne, Ellard, Sian, Hattersley, Andrew T., and Flanagan, Sarah E.
- Subjects
AUTOIMMUNE diseases ,DIABETES ,AUTOIMMUNITY ,MONOGENIC & polygenic inheritance (Genetics) ,EXOMES ,LYMPHOPROLIFERATIVE disorders ,CARRIER proteins ,CONSANGUINITY ,DISEASE susceptibility ,GENEALOGY ,GENES ,GENETIC techniques ,IMMUNITY ,TYPE 1 diabetes ,GENETIC mutation ,RESEARCH funding - Abstract
Young-onset autoimmune diabetes associated with additional autoimmunity usually reflects a polygenic predisposition, but rare cases result from monogenic autoimmunity. Diagnosing monogenic autoimmunity is crucial for patients' prognosis and clinical management. We sought to identify novel genetic causes of autoimmunity presenting with neonatal diabetes (NDM) (diagnosis <6 months). We performed exome sequencing in a patient with NDM and autoimmune lymphoproliferative syndrome and his unrelated, unaffected parents and identified compound heterozygous null mutations in LRBA Biallelic LRBA mutations cause common variable immunodeficiency-8; however, NDM has not been confirmed in this disorder. We sequenced LRBA in 169 additional patients with diabetes diagnosed <1 year without mutations in the 24 known NDM genes. We identified recessive null mutations in 8 additional probands, of which, 3 had NDM (<6 months). Diabetes was the presenting feature in 6 of 9 probands. Six of 17 (35%) patients born to consanguineous parents and with additional early-onset autoimmunity had recessive LRBA mutations. LRBA testing should be considered in patients with diabetes diagnosed <12 months, particularly if they have additional autoimmunity or are born to consanguineous parents. A genetic diagnosis is important as it can enable personalized therapy with abatacept, a CTLA-4 mimetic, and inform genetic counseling. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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34. The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease.
- Author
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Yi Shiau Ng, Alston, Charlotte L., Diodato, Daria, Morris, Andrew A., Ulrick, Nicole, Kmoch, Stanislav, Houštěk, Josef, Martinelli, Diego, Haghighi, Alireza, Atiq, Mehnaz, Gamero, Montserrat Anton, Garcia-Martinez, Elena, Kratochvílová, Hana, Santra, Saikat, Brown, Ruth M., Brown, Garry K., Ragge, Nicola, Monavari, Ahmad, Pysden, Karen, and Ravn, Kirstine
- Abstract
Background Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects. Methods We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors. Results We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, p.(Leu435Phe); c.830+1G>A and c.1317+1G>T. Together with all previously published cases (n=32), we show that congenital sensorineural deafness, hypotonia, developmental delay and lactic acidaemia are common clinical manifestations with disease onset under 2 years. Renal involvement is more prevalent than seizures (66% vs 44%). In addition, median survival time was longer in patients with renal involvement compared with those without renal disease (6 years vs 8 months, p=0.009). The neurological phenotype also appears milder in patients with renal involvement. Conclusions The clinical phenotypes and prognosis associated with RMND1 mutations are more heterogeneous than that were initially described. Regular monitoring of kidney function is imperative in the clinical practice in light of nephropathy being present in over 60% of cases. Furthermore, renal replacement therapy should be considered particularly in those patients with mild neurological manifestation as shown in our study that four recipients of kidney transplant demonstrate good clinical outcome to date. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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35. Sengers syndrome: six novel AGK mutations in seven new families and review of the phenotypic and mutational spectrum of 29 patients
- Author
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Haghighi, Alireza, primary, Haack, Tobias B, additional, Atiq, Mehnaz, additional, Mottaghi, Hassan, additional, Haghighi-Kakhki, Hamidreza, additional, Bashir, Rani A, additional, Ahting, Uwe, additional, Feichtinger, René G, additional, Mayr, Johannes A, additional, Rötig, Agnès, additional, Lebre, Anne-Sophie, additional, Klopstock, Thomas, additional, Dworschak, Andrea, additional, Pulido, Nathan, additional, Saeed, Mahmood A, additional, Saleh-Gohari, Nasrollah, additional, Holzerova, Eliska, additional, Chinnery, Patrick F, additional, Taylor, Robert W, additional, and Prokisch, Holger, additional
- Published
- 2014
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- View/download PDF
36. A Novel Missense Mutation in Oncostatin M Receptor Beta Causing Primary Localized Cutaneous Amyloidosis
- Author
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Saeedi, Marjan, primary, Ebrahim-Habibi, Azadeh, additional, Haghighi, Alireza, additional, Zarrabi, Fariba, additional, Amoli, Mahsa M., additional, and Robati, Reza M., additional
- Published
- 2014
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- View/download PDF
37. Identification of a SLC19A2 nonsense mutation in Persian families with thiamine-responsive megaloblastic anemia
- Author
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Setoodeh, Aria, primary, Haghighi, Amirreza, additional, Saleh-Gohari, Nasrollah, additional, Ellard, Sian, additional, and Haghighi, Alireza, additional
- Published
- 2013
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- View/download PDF
38. A Missense Mutation in the MBTPS2 Gene Underlies the X-Linked Form of Olmsted Syndrome
- Author
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Haghighi, Alireza, primary, Scott, Claire A., additional, Poon, Daniel S., additional, Yaghoobi, Reza, additional, Saleh-Gohari, Nasrollah, additional, Plagnol, Vincent, additional, and Kelsell, David P., additional
- Published
- 2013
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39. Analysis of the Antiproliferative Effects of Curcumin and Nanocurcumin in MDA-MB231 as a Breast Cancer Cell Line.
- Author
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Khosropanah, Mohammad Hossein, Dinarvand, Amin, Nezhadhosseini, Afsaneh, Haghighi, Alireza, Hashemi, Sima, Nirouzad, Fereidon, Khatamsaz, Sepideh, Entezari, Maliheh, Hashem, Mehrdad, and Dehghani, Hossein
- Subjects
CURCUMIN ,CHITOSAN ,NANOGELS ,NANOPARTICLES ,CELL lines ,TRANSMISSION electron microscopy - Abstract
Cancer is one of the main causes of mortality in the world which appears by the effect of enviromental physico-chemical mutagen and carcinogen agents. The identificat:ion of new cytotoxic drug with low sid effects on immune system has developed as important area in new studies of immunopharmacology. Curcumin is a natural polyphenol with anti-oxidative, anti-inflammatory and anti-cancer properties. Its therapeutic potential is substantially hindered by the rather low water solubility and bioavailability, hence the need for suitable carriers. In this report we employed nanogel-based nanoparticle approach to improve upon its effectiveness. Myristic acid-chitosan (MA-chitosan) nanogels were prepared by the technique of self-assembly. Curcumin was loaded into the nanogels. The surface morphology of the prepared nanoparticles was determined using SEM and TEM. The other objective of this study was to examine the in vitro cytotoxic activity of cell death of curcumin and nanocurcumin on human breast adenocarcinoma cell line (MDA-MB231). Cytotoxicity and viability of curcumin and nanocurcumin were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. Transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. Proliferation of MDA-MB231 cells was significantly inhibited by curcumin and nanocurcumin in a concentration-dependent manner in defined times. There were significant differences in IC 50 curcumin and nanocurcumin. curcumin -loaded nanoparticles proved more effective compared to TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the anticancer properties of curcumin -loaded nanoparticles. [ABSTRACT FROM AUTHOR]
- Published
- 2016
40. Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility
- Author
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Haghighi, Amirreza, primary, Haghighi, Alireza, additional, Setoodeh, Aria, additional, Saleh-Gohari, Nasrollah, additional, Astuti, Dewi, additional, and Barrett, Timothy G, additional
- Published
- 2012
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41. Identification of two HEXA mutations causing infantile-onset Tay–Sachs disease in the Persian population
- Author
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Haghighi, Alireza, primary, Rezazadeh, Jamileh, additional, Shadmehri, Azam Ahmadi, additional, Haghighi, Amirreza, additional, Kornreich, Ruth, additional, and Desnick, Robert J, additional
- Published
- 2011
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42. Genetics of GNE myopathy in the non-Jewish Persian population
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Haghighi, Alireza, Nafissi, Shahriar, Qurashi, Abrar, Tan, Zheng, Shamshiri, Hosein, Nilipour, Yalda, Haghighi, Amirreza, Desnick, Robert J, and Kornreich, Ruth
- Abstract
GNE myopathy is an autosomal recessive adult-onset disorder characterized by progressive muscle atrophy and weakness, initially involving the distal muscles, while often sparing the quadriceps. It is caused by variants in the GNE gene that encodes a key bifunctional enzyme in the sialic acid biosynthetic pathway. We investigated the clinical and molecular characteristics of 18 non-Jewish Persian patients from 11 unrelated GNE myopathy families. In addition, we reviewed the previously reported cases and suggest genotype–phenotype correlations for the identified variants. Comprehensive clinical and laboratory evaluations were carried out. Sequencing of the GNE gene was performed using genomic DNA from the patients. Screening of the identified variants was performed in all relevant family members. Molecular analyses identified three causative homozygous GNE variants in 11 families: c.2228T>C (p. M743T) in 7, c.830G>A (p.R277Q) in 2, and one novel variation (c.804G>A) in 2 families that results in a synonymous codon change (p.L268=) and likely creates a novel splice site affecting the protein function. This study confirms that c.2228T>C (p.M743T) is the most prevalent disease-causing variant in the non-Jewish Persian population, but other GNE variants can cause GNE myopathy in this population. The patients with all three different variants had similar ages of onset. The youngest patient was an 18-year-old girl in whom the c.830G>A (p.R277Q) variant was identified, whereas the oldest onset age (31 years) was seen in a male patient with c.804G>A (p.L268=). The results of this investigation expand our knowledge about the genotype–phenotype correlations in GNE myopathy and aid in clinical management and therapeutic interventions.
- Published
- 2016
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43. Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility.
- Author
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Haghighi, Amirreza, Haghighi, Alireza, Setoodeh, Aria, Saleh-Gohari, Nasrollah, Astuti, Dewi, and Barrett, Timothy G
- Subjects
- *
WOLFRAM syndrome , *HOMOZYGOSITY , *NEURODEGENERATION , *HUMAN fertility , *GENETIC counseling , *FAMILY planning - Abstract
Wolfram syndrome (WFS) is a neurodegenerative genetic condition characterized by juvenile-onset of diabetes mellitus and optic atrophy. We studied clinical features and the molecular basis of severe WFS (neurodegenerative complications) in two consanguineous families from Iran. A clinical and molecular genetic investigation was performed in the affected and healthy members of two families. The clinical diagnosis of WFS was confirmed by the existence of diabetes mellitus and optic atrophy in the affected patients, who in addition had severe neurodegenerative complications. Sequencing of WFS1 was undertaken in one affected member from each family. Targeted mutations were tested in all members of relevant families. Patients had most of the reported features of WFS. Two affected males in the first family had fathered unaffected children. We identified two homozygous mutations previously reported with apparently milder phenotypes: family 1: c.631G>A (p.Asp211Asn) in exon 5, and family 2: c.1456C>T (p.Gln486*) in exon 8. Heterozygous carriers were unaffected. This is the first report of male Wolfram patients who have successfully fathered children. Surprisingly, they also had almost all the complications associated with WFS. Our report has implications for genetic counseling and family planning advice for other affected families. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
44. Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy
- Author
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Hinson, John Travis, Chopra, Anant, Nafissi, N., Polacheck, William, Benson, Craig Carlyle, Swist, S., Gorham, Joshua McClean, Yang, Luhan, Schafer, S., Sheng, Calvin Chen, Haghighi, Alireza, Homsy, Jason George, Hubner, N., Church, George McDonald, Cook, S. A., Linke, Wolfgang, Chen, Christopher, Seidman, Jonathan G., and Seidman, Christine Edry
- Abstract
Human mutations that truncate the massive sarcomere protein titin [TTN-truncating variants (TTNtvs)] are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtvs, diminish contractile performance and are pathogenic. By combining functional analyses with RNA sequencing, we explain why truncations in the A-band domain of TTN cause DCM, whereas truncations in the I band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS cell–derived cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and β-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodeling.
- Published
- 2015
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45. Senior-Loken syndrome secondary to NPHP5/IQCB1 mutation in an Iranian family.
- Author
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Haghighi, Alireza, Al-Hamed, Mohamed, Al-Hissi, Safa, Hynes, Ann-Marie, Sharifian, Maryam, Roozbeh, Jamshid, Saleh-Gohari, Nasrollah, and Sayer, John A.
- Subjects
- *
RARE diseases , *IRANIANS , *GENETIC mutation , *KIDNEY diseases , *GENETIC disorders , *RETINAL degeneration , *MOLECULAR genetics , *DIAGNOSIS , *GENETICS , *DISEASES - Abstract
Senior-Loken syndrome (SLS) is a rare autosomal recessive disease characterized by nephronophthisis and early-onset retinal degeneration. We used a large Iranian family with SLS to establish a molecular genetic diagnosis. Following clinical evaluation, we undertook homozygosity mapping in two affected family members and mutational analysis in known SLS genes coinciding with regions of homozygosity. In a region of homozygosity coinciding with a known SLS locus on chromosome 3q21.1, we found a homozygous non-sense mutation R332X in NPHP5/IQCB1. This is the first report of a molecular genetic diagnosis in an Iranian kindred with SLS. [ABSTRACT FROM PUBLISHER]
- Published
- 2011
46. Homozygosity Mapping and Whole Exome Sequencing Reveal a Novel Homozygous COL18A1 Mutation Causing Knobloch Syndrome
- Author
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Haghighi, Alireza, Tiwari, Amit, Piri, Niloofar, Nürnberg, Gudrun, Saleh-Gohari, Nasrollah, Haghighi, Amirreza, Neidhardt, John, Nürnberg, Peter, and Berger, Wolfgang
- Subjects
3. Good health - Abstract
The aim of this study was to identify the genetic basis of a chorioretinal dystrophy with high myopia of unknown origin in a child of a consanguineous marriage. The proband and ten family members of Iranian ancestry participated in this study. Linkage analysis was carried out with DNA samples of the proband and her parents by using the Human SNP Array 6.0. Whole exome sequencing (WES) was performed with the patients’ DNA. Specific sequence alterations within the homozygous regions identified by whole exome sequencing were verified by Sanger sequencing. Upon genetic analysis, a novel homozygous frameshift mutation was found in exon 42 of the COL18A1 gene in the patient. Both parents were heterozygous for this sequence variation. Mutations in COL18A1 are known to cause Knobloch syndrome (KS). Retrospective analysis of clinical records of the patient revealed surgical removal of a meningocele present at birth. The clinical features shown by our patient were typical of KS with the exception of chorioretinal degeneration which is a rare manifestation. This is the first case of KS reported in a family of Iranian ancestry. We identified a novel disease-causing (deletion) mutation in the COL18A1 gene leading to a frameshift and premature stop codon in the last exon. The mutation was not present in SNP databases and was also not found in 192 control individuals. Its localization within the endostatin domain implicates a functional relevance of endostatin in KS. A combined approach of linkage analysis and WES led to a rapid identification of the disease-causing mutation even though the clinical description was not completely clear at the beginning., PLoS ONE, 9 (11), ISSN:1932-6203
47. Erratum. Recessively Inherited Mutations Cause Autoimmunity Presenting as Neonatal Diabetes. Diabetes 2017;66:2316-2322.
- Author
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Johnson, Matthew B, De Franco, Elisa, Lango Allen, Hana, Al Senani, Aisha, Elbarbary, Nancy, Siklar, Zeynep, Berberoglu, Merih, Imane, Zineb, Haghighi, Alireza, Razavi, Zahra, Ullah, Irfan, Alyaarubi, Saif, Gardner, Daphne, Ellard, Sian, Hattersley, Andrew T, and Flanagan, Sarah E
- Published
- 2018
- Full Text
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48. Homozygosity Mapping and Whole Exome Sequencing Reveal a Novel Homozygous COL18A1 Mutation Causing Knobloch Syndrome
- Author
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John Neidhardt, Gudrun Nürnberg, Wolfgang Berger, Amit Tiwari, Niloofar Piri, Nasrollah Saleh-Gohari, Amirreza Haghighi, Alireza Haghighi, Peter Nürnberg, University of Zurich, Haghighi, Alireza, and Haghighi, Amirreza
- Subjects
Male ,Proband ,Heredity ,Genetic Linkage ,Molecular biology ,lcsh:Medicine ,Iran ,Blindness ,Bioinformatics ,Collagen Type XIII ,Homozygosity ,11124 Institute of Medical Molecular Genetics ,Consanguinity ,Sequencing techniques ,Medicine and Health Sciences ,Myopia ,Knobloch syndrome ,Protein Isoforms ,Exome ,Autosomal Linkage ,DNA sequencing ,lcsh:Science ,Child ,Frameshift Mutation ,Exome sequencing ,Encephalocele ,Visual Impairments ,Genetics ,Sanger sequencing ,Multidisciplinary ,Homozygote ,Retinal Degeneration ,Retinal dystrophy ,Chromosome Mapping ,Genomics ,Disease gene identification ,Pedigree ,3. Good health ,Codon, Nonsense ,symbols ,Retinal Disorders ,Female ,Transcriptome Analysis ,Linkage analysis ,Research Article ,SNP array ,Next-Generation Sequencing ,Heterozygote ,Molecular Sequence Data ,610 Medicine & health ,1100 General Agricultural and Biological Sciences ,Biology ,Human Genomics ,Chromosomal Inheritance ,Frameshift mutation ,Molecular Genetics ,symbols.namesake ,1300 General Biochemistry, Genetics and Molecular Biology ,medicine ,Humans ,Inherited Eye Disorders ,1000 Multidisciplinary ,Base Sequence ,Biology and life sciences ,Genome, Human ,lcsh:R ,High Throughput Sequencing ,Whole exome sequencing ,Retinal Detachment ,Dideoxy DNA sequencing ,Computational Biology ,Sequence Analysis, DNA ,Genome Analysis ,medicine.disease ,Ophthalmology ,Molecular biology techniques ,Mutation ,570 Life sciences ,biology ,lcsh:Q - Abstract
The aim of this study was to identify the genetic basis of a chorioretinal dystrophy with high myopia of unknown origin in a child of a consanguineous marriage. The proband and ten family members of Iranian ancestry participated in this study. Linkage analysis was carried out with DNA samples of the proband and her parents by using the Human SNP Array 6.0. Whole exome sequencing (WES) was performed with the patients’ DNA. Specific sequence alterations within the homozygous regions identified by whole exome sequencing were verified by Sanger sequencing. Upon genetic analysis, a novel homozygous frameshift mutation was found in exon 42 of the COL18A1 gene in the patient. Both parents were heterozygous for this sequence variation. Mutations in COL18A1 are known to cause Knobloch syndrome (KS). Retrospective analysis of clinical records of the patient revealed surgical removal of a meningocele present at birth. The clinical features shown by our patient were typical of KS with the exception of chorioretinal degeneration which is a rare manifestation. This is the first case of KS reported in a family of Iranian ancestry. We identified a novel disease-causing (deletion) mutation in the COL18A1 gene leading to a frameshift and premature stop codon in the last exon. The mutation was not present in SNP databases and was also not found in 192 control individuals. Its localization within the endostatin domain implicates a functional relevance of endostatin in KS. A combined approach of linkage analysis and WES led to a rapid identification of the disease-causing mutation even though the clinical description was not completely clear at the beginning. ISSN:1932-6203
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- 2014
49. Contribution of Noncanonical Splice Variants to TTN Truncating Variant Cardiomyopathy.
- Author
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Patel PN, Ito K, Willcox JAL, Haghighi A, Jang MY, Gorham JM, DePalma SR, Lam L, McDonough B, Johnson R, Lakdawala NK, Roberts A, Barton PJR, Cook SA, Fatkin D, Seidman CE, and Seidman JG
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- Adolescent, Adult, Female, Humans, Male, Middle Aged, Cardiomyopathy, Dilated genetics, Connectin genetics, Exons, Heterozygote, RNA Splicing
- Abstract
Background: Heterozygous TTN truncating variants cause 10% to 20% of idiopathic dilated cardiomyopathy (DCM). Although variants which disrupt canonical splice signals (ie, invariant dinucleotide of the splice donor site, invariant dinucleotide of the splice acceptor site) at exon-intron junctions are readily recognized as TTN truncating variants, the effects of other nearby sequence variations on splicing and their contribution to disease is uncertain., Methods: Rare variants of unknown significance located in the splice regions of highly expressed TTN exons from 203 DCM cases, 3329 normal subjects, and clinical variant databases were identified. The effects of these variants on splicing were assessed using an in vitro splice assay., Results: Splice-altering variants of unknown significance were enriched in DCM cases over controls and present in 2% of DCM patients ( P =0.002). Application of this method to clinical variant databases demonstrated 20% of similar variants of unknown significance in TTN splice regions affect splicing. Noncanonical splice-altering variants were most frequently located at position +5 of the donor site ( P =4.4×10
7 ) and position -3 of the acceptor site ( P =0.002). SpliceAI, an emerging in silico prediction tool, had a high positive predictive value (86%-95%) but poor sensitivity (15%-50%) for the detection of splice-altering variants. Alternate exons spliced out of most TTN transcripts frequently lacked the consensus base at +5 donor and -3 acceptor positions., Conclusions: Noncanonical splice-altering variants in TTN explain 1-2% of DCM and offer a 10-20% increase in the diagnostic power of TTN sequencing in this disease. These data suggest rules that may improve efforts to detect splice-altering variants in other genes and may explain the low percent splicing observed for many alternate TTN exons.- Published
- 2021
- Full Text
- View/download PDF
50. Genetic and Phenotypic Landscape of Peripartum Cardiomyopathy.
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Goli R, Li J, Brandimarto J, Levine LD, Riis V, McAfee Q, DePalma S, Haghighi A, Seidman JG, Seidman CE, Jacoby D, Macones G, Judge DP, Rana S, Margulies KB, Cappola TP, Alharethi R, Damp J, Hsich E, Elkayam U, Sheppard R, Alexis JD, Boehmer J, Kamiya C, Gustafsson F, Damm P, Ersbøll AS, Goland S, Hilfiker-Kleiner D, McNamara DM, and Arany Z
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- Adult, Cardiomyopathies physiopathology, Female, Humans, Phenotype, Pregnancy, Retrospective Studies, Cardiomyopathies genetics, Peripartum Period genetics
- Abstract
Background: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM., Methods: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN , and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated., Results: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [ P *]=1.2×10
-46 ). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P *=7.0×10-8 ), DSP (odds ratio=14.9, P *=1.0×10-8 ), and BAG3 (odds ratio=53.1, P *=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P =2.5×10-4 ), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery., Conclusions: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.- Published
- 2021
- Full Text
- View/download PDF
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