Catalytic Ozonation Using Edge-Hydroxylated Graphite-Based Materials

"This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Sustainable Chemistry & Engineering, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acssuschemeng.9b04646"[EN] This work reports the catalytic ozonation activity of high surface area graphite materials selectively functionalized at the edges with hydroxyl groups. The graphite-based catalyst shows higher activity than the parent graphite, commercial activated carbon, commercial multiwall carbon nanotubes, commercial diamond nanoparticles, graphene oxide, or reduced graphene oxide. Importantly, the catalytic activity of the graphite-based material is also higher than those of benchmark ozonation catalysts such as Co3O4 or Fe2O3. The graphite catalyst was reused up to 10 times with only a minor decrease in the catalytic activity. Catalytic activation of O-3 leads to the generation of hydroperoxide radicals and O-1(2). These results have been interpreted as derived from the combination of a suitable work function and the presence of phenolic/semiquinone-like redox pairs, as well as high dispersibility in water due to the presence of -OH groups. This work highlights the possibility of engineering active and stable carbocatalysts for reactions typically promoted by transition metals.Financial support by the Spanish Ministry of Science and Innovation (Severn Ochoa and RTI2018-098237-CO21) and Generalitat Valenciana (Prometeo 2017/083) is gratefully acknowledged. S.N. is thankful for financial support from the Fundacion Ramon Areces (XVIII Concurso Nacional para la Adjudication de Ayudas a la Investigacion en Ciencias de la Vida y de la Materia, 2016), Ministerio de Ciencia, Innovacion y Universidades RTI2018-099482-A-I00 project and Generalitat Valenciana grupos de investigacion consolidables 2019 (ref: AICO/2019/214) project.Bernat-Quesada, F.; Espinosa-López, JC.; Barbera, V.; Alvaro Rodríguez, MM.; Galimberti, M.; Navalón Oltra, S.; García Gómez, H. (2019). Catalytic Ozonation Using Edge-Hydroxylated Graphite-Based Materials. ACS Sustainable Chemistry & Engineering. 7(20):17443-17452. https://doi.org/10.1021/acssuschemeng.9b04646S174431745272

Engineering of activated carbon surface to enhance the catalytic activity of supported cobalt oxide nanoparticles in peroxymonosulfate activation

[EN] Commercial activated carbon has been functionalized by chemical or thermal treatments to introduce surface oxygen functional groups able to anchor small cobalt nanoparticles with superior catalytic activity for peroxymonosulfate activation. The resulting activated carbon supports where characterized by combustion elemental analysis, Fourier-transformed infrared spectroscopy, Raman spectroscopy, isothermal N-2 adsorption, temperature programmed desorption/mass spectrometry, X-ray diffraction and scanning electron microscopy. Activated carbon functionalization by nitric acid resulted the most appropriated method to provide a higher population of oxygenated functional groups able to anchor small cobalt nanoparticles. The catalytic activity of supported oxidized metal nanoparticles (4.7 +/- 0.05 nm) was higher than analogous non-oxidized cobalt nanoparticles (2.9 +/- 0.14 nm). The use of analogous supported oxidized iron or copper nanoparticles resulted in lower catalytic activity. Importantly, the supported oxidized cobalt nanoparticles at 0.2 wt% loading exhibit higher activity than benchmark catalysts such as unsupported Co3O4 solid or even homogeneous Co2+ ions. This is a reflection of the relatively low estimated activation energy for both processes, peroxymonosulfate decomposition and phenol degradation. The estimated activation energy values are about 30 and 32 kJ mol(-1). The stability of the most active catalyst was assessed by performing eight consecutive uses without observing decrease of catalytic activity, neither metal leaching or metal nanoparticle aggregation. Turnover numbers/turnover frequencies values as high as 440(5)/8.10(5)h(-1) for peroxymonosulfate activation and 39.10(3)/68.10(3) h(-1) for phenol degradation at pH 7 and 20 degrees C have been estimated, respectively. Electron paramagnetic resonance measurements and selective quenching experiments revealed that the generated sulfate radicals from peroxymonosulfate rapidly are transformed in highly reactive hydroxyl radicals. In excellent agreement with previous reports, this work demonstrates the importance of an adequate activated carbon functionalization to obtain superior and stable catalysts for peroxymonosulfate activation.Financial support by the Spanish Ministry of Economy and Competitiveness (Severo Ochoa, CTQ2015-65963-CQ-R1) and CTQ2014-53292-R is gratefully acknowledged. Generalitat Valenciana is also thanked for funding (Prometeo 2017/083). S.N. thanks financial support by the Fundacion Ramon Areces (XVIII Concurso Nacional para la Adjudicacion de Ayudas a la Investigacion en Ciencias de la Vida y de la Materia, 2016).Espinosa-López, JC.; Manickam-Periyaraman, P.; Bernat-Quesada, F.; Sivanesan, S.; Alvaro Rodríguez, MM.; García Gómez, H.; Navalón Oltra, S. (2019). Engineering of activated carbon surface to enhance the catalytic activity of supported cobalt oxide nanoparticles in peroxymonosulfate activation. Applied Catalysis B Environmental. 249:42-53. https://doi.org/10.1016/j.apcatb.2019.02.043S425324

Lethal congenital contracture syndrome 11: A case report and literature review

Lethal congenital contracture syndrome 11 (LCCS11) is caused by homozygous or compound heterozygous variants in the GLDN gene on chromosome 15q21. GLDN encodes gliomedin, a protein required for the formation of the nodes of Ranvier and development of the human peripheral nervous system. We report a fetus with ultrasound alterations detected at 28 weeks of gestation. The fetus exhibited hydrops, short long bones, fixed limb joints, absent fetal movements, and polyhydramnios. The pregnancy was terminated and postmortem studies confirmed the prenatal findings: distal arthrogryposis, fetal growth restriction, pulmonary hypoplasia, and retrognathia. The fetus had a normal chromosomal microarray analysis. Exome sequencing revealed two novel compound heterozygous variants in the GLDN associated with LCCS11. This manuscript reports this case and performs a literature review of all published LCCS11 cases

Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer's Disease Patients: Clinical, Neuroimaging and Neuropathological Findings

In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene.This work was supported by the Instituto de Salud Carlos III (PI17/01067) and AGAUR from the Autonomous Catalan Government (2017SGR1134). Dr. Víctor Antonio Blanco-Palmero is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Biomedical Research Institute) through a “Río Hortega” contract (CM18/0095). Dr. Sara Llamas-Velasco is supported by the Instituto de Salud Carlos III (ISCIII; Spanish Biomedical Research Institute) through a “Juan Rodés” contract (JR 18/00046).S

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Taking the pulse of Earth's tropical forests using networks of highly distributed plots

Tropical forests are the most diverse and productive ecosystems on Earth. While better understanding of these forests is critical for our collective future, until quite recently efforts to measure and monitor them have been largely disconnected. Networking is essential to discover the answers to questions that transcend borders and the horizons of funding agencies. Here we show how a global community is responding to the challenges of tropical ecosystem research with diverse teams measuring forests tree-by-tree in thousands of long-term plots. We review the major scientific discoveries of this work and show how this process is changing tropical forest science. Our core approach involves linking long-term grassroots initiatives with standardized protocols and data management to generate robust scaled-up results. By connecting tropical researchers and elevating their status, our Social Research Network model recognises the key role of the data originator in scientific discovery. Conceived in 1999 with RAINFOR (South America), our permanent plot networks have been adapted to Africa (AfriTRON) and Southeast Asia (T-FORCES) and widely emulated worldwide. Now these multiple initiatives are integrated via ForestPlots.net cyber-infrastructure, linking colleagues from 54 countries across 24 plot networks. Collectively these are transforming understanding of tropical forests and their biospheric role. Together we have discovered how, where and why forest carbon and biodiversity are responding to climate change, and how they feedback on it. This long-term pan-tropical collaboration has revealed a large long-term carbon sink and its trends, as well as making clear which drivers are most important, which forest processes are affected, where they are changing, what the lags are, and the likely future responses of tropical forests as the climate continues to change. By leveraging a remarkably old technology, plot networks are sparking a very modern revolution in tropical forest science. In the future, humanity can benefit greatly by nurturing the grassroots communities now collectively capable of generating unique, long-term understanding of Earth's most precious forests.Additional co-authors: Susan Laurance, William Laurance, Francoise Yoko Ishida, Andrew Marshall, Catherine Waite, Hannsjoerg Woell, Jean-Francois Bastin, Marijn Bauters, Hans Beeckman, Pfascal Boeckx, Jan Bogaert, Charles De Canniere, Thales de Haulleville, Jean-Louis Doucet, Olivier Hardy, Wannes Hubau, Elizabeth Kearsley, Hans Verbeeck, Jason Vleminckx, Steven W. Brewer, Alfredo Alarcón, Alejandro Araujo-Murakami, Eric Arets, Luzmila Arroyo, Ezequiel Chavez, Todd Fredericksen, René Guillén Villaroel, Gloria Gutierrez Sibauty, Timothy Killeen, Juan Carlos Licona, John Lleigue, Casimiro Mendoza, Samaria Murakami, Alexander Parada Gutierrez, Guido Pardo, Marielos Peña-Claros, Lourens Poorter, Marisol Toledo, Jeanneth Villalobos Cayo, Laura Jessica Viscarra, Vincent Vos, Jorge Ahumada, Everton Almeida, Jarcilene Almeida, Edmar Almeida de Oliveira, Wesley Alves da Cruz, Atila Alves de Oliveira, Fabrício Alvim Carvalho, Flávio Amorim Obermuller, Ana Andrade, Fernanda Antunes Carvalho, Simone Aparecida Vieira, Ana Carla Aquino, Luiz Aragão, Ana Claudia Araújo, Marco Antonio Assis, Jose Ataliba Mantelli Aboin Gomes, Fabrício Baccaro, Plínio Barbosa de Camargo, Paulo Barni, Jorcely Barroso, Luis Carlos Bernacci, Kauane Bordin, Marcelo Brilhante de Medeiros, Igor Broggio, José Luís Camargo, Domingos Cardoso, Maria Antonia Carniello, Andre Luis Casarin Rochelle, Carolina Castilho, Antonio Alberto Jorge Farias Castro, Wendeson Castro, Sabina Cerruto Ribeiro, Flávia Costa, Rodrigo Costa de Oliveira, Italo Coutinho, John Cunha, Lola da Costa, Lucia da Costa Ferreira, Richarlly da Costa Silva, Marta da Graça Zacarias Simbine, Vitor de Andrade Kamimura, Haroldo Cavalcante de Lima, Lia de Oliveira Melo, Luciano de Queiroz, José Romualdo de Sousa Lima, Mário do Espírito Santo, Tomas Domingues, Nayane Cristina dos Santos Prestes, Steffan Eduardo Silva Carneiro, Fernando Elias, Gabriel Eliseu, Thaise Emilio, Camila Laís Farrapo, Letícia Fernandes, Gustavo Ferreira, Joice Ferreira, Leandro Ferreira, Socorro Ferreira, Marcelo Fragomeni Simon, Maria Aparecida Freitas, Queila S. García, Angelo Gilberto Manzatto, Paulo Graça, Frederico Guilherme, Eduardo Hase, Niro Higuchi, Mariana Iguatemy, Reinaldo Imbrozio Barbosa, Margarita Jaramillo, Carlos Joly, Joice Klipel, Iêda Leão do Amaral, Carolina Levis, Antonio S. Lima, Maurício Lima Dan, Aline Lopes, Herison Madeiros, William E. Magnusson, Rubens Manoel dos Santos, Beatriz Marimon, Ben Hur Marimon Junior, Roberta Marotti Martelletti Grillo, Luiz Martinelli, Simone Matias Reis, Salomão Medeiros, Milton Meira-Junior, Thiago Metzker, Paulo Morandi, Natanael Moreira do Nascimento, Magna Moura, Sandra Cristina Müller, Laszlo Nagy, Henrique Nascimento, Marcelo Nascimento, Adriano Nogueira Lima, Raimunda Oliveira de Araújo, Jhonathan Oliveira Silva, Marcelo Pansonato, Gabriel Pavan Sabino, Karla Maria Pedra de Abreu, Pablo José Francisco Pena Rodrigues, Maria Piedade, Domingos Rodrigues, José Roberto Rodrigues Pinto, Carlos Quesada, Eliana Ramos, Rafael Ramos, Priscyla Rodrigues, Thaiane Rodrigues de Sousa, Rafael Salomão, Flávia Santana, Marcos Scaranello, Rodrigo Scarton Bergamin, Juliana Schietti, Jochen Schöngart, Gustavo Schwartz, Natalino Silva, Marcos Silveira, Cristiana Simão Seixas, Marta Simbine, Ana Claudia Souza, Priscila Souza, Rodolfo Souza, Tereza Sposito, Edson Stefani Junior, Julio Daniel do Vale, Ima Célia Guimarães Vieira, Dora Villela, Marcos Vital, Haron Xaud, Katia Zanini, Charles Eugene Zartman, Nur Khalish Hafizhah Ideris, Faizah binti Hj Metali, Kamariah Abu Salim, Muhd Shahruney Saparudin, Rafizah Mat Serudin, Rahayu Sukmaria Sukri, Serge Begne, George Chuyong, Marie Noel Djuikouo, Christelle Gonmadje, Murielle Simo-Droissart, Bonaventure Sonké, Hermann Taedoumg, Lise Zemagho, Sean Thomas, Fidèle Baya, Gustavo Saiz, Javier Silva Espejo, Dexiang Chen, Alan Hamilton, Yide Li, Tushou Luo, Shukui Niu, Han Xu, Zhang Zhou, Esteban Álvarez-Dávila, Juan Carlos Andrés Escobar, Henry Arellano-Peña, Jaime Cabezas Duarte, Jhon Calderón, Lina Maria Corrales Bravo, Borish Cuadrado, Hermes Cuadros, Alvaro Duque, Luisa Fernanda Duque, Sandra Milena Espinosa, Rebeca Franke-Ante, Hernando García, Alejandro Gómez, Roy González-M., Álvaro Idárraga-Piedrahíta, Eliana Jimenez, Rubén Jurado, Wilmar López Oviedo, René López-Camacho, Omar Aurelio Melo Cruz, Irina Mendoza Polo, Edwin Paky, Karen Pérez, Angel Pijachi, Camila Pizano, Adriana Prieto, Laura Ramos, Zorayda Restrepo Correa, James Richardson, Elkin Rodríguez, Gina M. Rodriguez M., Agustín Rudas, Pablo Stevenson, Markéta Chudomelová, Martin Dancak, Radim Hédl, Stanislav Lhota, Martin Svatek, Jacques Mukinzi, Corneille Ewango, Terese Hart, Emmanuel Kasongo Yakusu, Janvier Lisingo, Jean-Remy Makana, Faustin Mbayu, Benjamin Toirambe, John Tshibamba Mukendi, Lars Kvist, Gustav Nebel, Selene Báez, Carlos Céron, Daniel M. Griffith, Juan Ernesto Guevara Andino, David Neill, Walter Palacios, Maria Cristina Peñuela-Mora, Gonzalo Rivas-Torres, Gorky Villa, Sheleme Demissie, Tadesse Gole, Techane Gonfa, Kalle Ruokolainen, Michel Baisie, Fabrice Bénédet, Wemo Betian, Vincent Bezard, Damien Bonal, Jerôme Chave, Vincent Droissart, Sylvie Gourlet-Fleury, Annette Hladik, Nicolas Labrière, Pétrus Naisso, Maxime Réjou-Méchain, Plinio Sist, Lilian Blanc, Benoit Burban, Géraldine Derroire, Aurélie Dourdain, Clement Stahl, Natacha Nssi Bengone, Eric Chezeaux, Fidèle Evouna Ondo, Vincent Medjibe, Vianet Mihindou, Lee White, Heike Culmsee, Cristabel Durán Rangel, Viviana Horna, Florian Wittmann, Stephen Adu-Bredu, Kofi Affum-Baffoe, Ernest Foli, Michael Balinga, Anand Roopsind, James Singh, Raquel Thomas, Roderick Zagt, Indu K. Murthy, Kuswata Kartawinata, Edi Mirmanto, Hari Priyadi, Ismayadi Samsoedin, Terry Sunderland, Ishak Yassir, Francesco Rovero, Barbara Vinceti, Bruno Hérault, Shin-Ichiro Aiba, Kanehiro Kitayama, Armandu Daniels, Darlington Tuagben, John T. Woods, Muhammad Fitriadi, Alexander Karolus, Kho Lip Khoon, Noreen Majalap, Colin Maycock, Reuben Nilus, Sylvester Tan, Almeida Sitoe, Indiana Coronado G., Lucas Ojo, Rafael de Assis, Axel Dalberg Poulsen, Douglas Sheil, Karen Arévalo Pezo, Hans Buttgenbach Verde, Victor Chama Moscoso, Jimmy Cesar Cordova Oroche, Fernando Cornejo Valverde, Massiel Corrales Medina, Nallaret Davila Cardozo, Jano de Rutte Corzo, Jhon del Aguila Pasquel, Gerardo Flores Llampazo, Luis Freitas, Darcy Galiano Cabrera, Roosevelt García Villacorta, Karina Garcia Cabrera, Diego García Soria, Leticia Gatica Saboya, Julio Miguel Grandez Rios, Gabriel Hidalgo Pizango, Eurídice Honorio Coronado, Isau Huamantupa-Chuquimaco, Walter Huaraca Huasco, Yuri Tomas Huillca Aedo, Jose Luis Marcelo Peña, Abel Monteagudo Mendoza, Vanesa Moreano Rodriguez, Percy Núñez Vargas, Sonia Cesarina Palacios Ramos, Nadir Pallqui Camacho, Antonio Peña Cruz, Freddy Ramirez Arevalo, José Reyna Huaymacari, Carlos Reynel Rodriguez, Marcos Antonio Ríos Paredes, Lily Rodriguez Bayona, Rocio del Pilar Rojas Gonzales, Maria Elena Rojas Peña, Norma Salinas Revilla, Yahn Carlos Soto Shareva, Raul Tupayachi Trujillo, Luis Valenzuela Gamarra, Rodolfo Vasquez Martinez, Jim Vega Arenas, Christian Amani, Suspense Averti Ifo, Yannick Bocko, Patrick Boundja, Romeo Ekoungoulou, Mireille Hockemba, Donatien Nzala, Alusine Fofanah, David Taylor, Guillermo Bañares-de Dios, Luis Cayuela, Íñigo Granzow-de la Cerda, Manuel Macía, Juliana Stropp, Maureen Playfair, Verginia Wortel, Toby Gardner, Robert Muscarella, Hari Priyadi, Ervan Rutishauser, Kuo-Jung Chao, Pantaleo Munishi, Olaf Bánki, Frans Bongers, Rene Boot, Gabriella Fredriksson, Jan Reitsma, Hans ter Steege, Tinde van Andel, Peter van de Meer, Peter van der Hout, Mark van Nieuwstadt, Bert van Ulft, Elmar Veenendaal, Ronald Vernimmen, Pieter Zuidema, Joeri Zwerts, Perpetra Akite, Robert Bitariho, Colin Chapman, Eilu Gerald, Miguel Leal, Patrick Mucunguzi, Miguel Alexiades, Timothy R. Baker, Karina Banda, Lindsay Banin, Jos Barlow, Amy Bennett, Erika Berenguer, Nicholas Berry, Neil M. Bird, George A. Blackburn, Francis Brearley, Roel Brienen, David Burslem, Lidiany Carvalho, Percival Cho, Fernanda Coelho, Murray Collins, David Coomes, Aida Cuni-Sanchez, Greta Dargie, Kyle Dexter, Mat Disney, Freddie Draper, Muying Duan, Adriane Esquivel-Muelbert, Robert Ewers, Belen Fadrique, Sophie Fauset, Ted R. Feldpausch, Filipe França, David Galbraith, Martin Gilpin, Emanuel Gloor, John Grace, Keith Hamer, David Harris, Tommaso Jucker, Michelle Kalamandeen, Bente Klitgaard, Aurora Levesley, Simon L. Lewis, Jeremy Lindsell, Gabriela Lopez-Gonzalez, Jon Lovett, Yadvinder Malhi, Toby Marthews, Emma McIntosh, Karina Melgaço, William Milliken, Edward Mitchard, Peter Moonlight, Sam Moore, Alexandra Morel, Julie Peacock, Kelvin Peh, Colin Pendry, R. Toby Pennington, Luciana de Oliveira Pereira, Carlos Peres, Oliver L. Phillips, Georgia Pickavance, Thomas Pugh, Lan Qie, Terhi Riutta, Katherine Roucoux, Casey Ryan, Tiina Sarkinen, Camila Silva Valeria, Dominick Spracklen, Suzanne Stas, Martin Sullivan, Michael Swaine, Joey Talbot, James Taplin, Geertje van der Heijden, Laura Vedovato, Simon Willcock, Mathew Williams, Luciana Alves, Patricia Alvarez Loayza, Gabriel Arellano, Cheryl Asa, Peter Ashton, Gregory Asner, Terry Brncic, Foster Brown, Robyn Burnham, Connie Clark, James Comiskey, Gabriel Damasco, Stuart Davies, Tony Di Fiore, Terry Erwin, William Farfan-Rios, Jefferson Hall, David Kenfack, Thomas Lovejoy, Roberta Martin, Olga Martha Montiel, John Pipoly, Nigel Pitman, John Poulsen, Richard Primack, Miles Silman, Marc Steininger, Varun Swamy, John Terborgh, Duncan Thomas, Peter Umunay, Maria Uriarte, Emilio Vilanova Torre, Ophelia Wang, Kenneth Young, Gerardo A. Aymard C., Lionel Hernández, Rafael Herrera Fernández, Hirma Ramírez-Angulo, Pedro Salcedo, Elio Sanoja, Julio Serrano, Armando Torres-Lezama, Tinh Cong Le, Trai Trong Le, Hieu Dang Tra

Early-Onset Dementia Associated with a Heterozygous, Nonsense, and de novo Variant in the MBD5 Gene

The haploinsufficiency of the methyl-binding domain protein 5 (MBD5) gene has been identified as the determinant cause of the neuropsychiatric disorders grouped under the name MBD5-neurodevelopment disorders (MAND). MAND includes patients with intellectual disability, behavioral problems, and seizures with a static clinical course. However, a few reports have suggested regression. We describe a non-intellectually disabled female, with previous epilepsy and personality disorder, who developed early-onset dementia. The extensive etiologic study revealed a heterozygous nonsense de novo pathogenic variant in the MBD5 gene. This finding could support including the MBD5 gene in the study of patients with atypical early-onset dementia. © 2021 - IOS Press. All rights reserved

Fragile X Syndrome Caused by Maternal Somatic Mosaicism of <i>FMR1</i> Gene: Case Report and Literature Review

Fragile X syndrome (FXS) is caused by an abnormal expansion of the number of trinucleotide CGG repeats located in the 5′ UTR in the first exon of the FMR1 gene. Size and methylation mosaicisms are commonly observed in FXS patients. Both types of mosaicisms might be associated with less severe phenotypes depending on the number of cells expressing FMRP. Although this dynamic mutation is the main underlying cause of FXS, other mechanisms, including point mutations or deletions, can lead to FXS. Several reports have demonstrated that de novo deletions including the entire or a portion of the FMR1 gene end up with the absence of FMRP and, thus, can lead to the typical clinical features of FXS. However, very little is known about the clinical manifestations associated with FMR1 gene deletions in mosaicism. Here, we report an FXS case caused by an entire hemizygous deletion of the FMR1 gene caused by maternal mosaicism. This manuscript reports this case and a literature review of the clinical manifestations presented by carriers of FMR1 gene deletions in mosaicism

Expanding the clinical and genetic spectrum of SQSTM1-related disorders in family with personality disorder and frontotemporal dementia

Objective:SQSTM1-variants associated with frontotemporal lobar degeneration have been described recently. In this study, we investigated a heterozygous in-frame duplication c.436_462dup p. (Pro146_Cys154dup) in the SQSTM1 gene in a family with a new phenotype characterized by a personality disorder and behavioral variant frontotemporal dementia (bvFTD). We review the literature on frontotemporal dementia (FTD) associated with SQSTM1. Methods: The index case and relatives were described, and a genetic study through Whole Exome Sequencing was performed. The literature was reviewed using Medline and Web of Science. Case reports, case series, and cohort studies were included if they provided information on SQSTM1 mutations associated with FTD. Results: Our patient is a 70-year-old man with a personality disorder since youth, familial history of dementia, and personality disorders with a 10-year history of cognitive decline and behavioral disturbances. A diagnosis of probable bvFTD was established, and the in-frame duplication c.436_462dup in the SQSTM1 gene was identified. Segregation analysis in the family confirmed that both affected sons with personality disorder were heterozygous carriers, but not his healthy 65-year-old brother. A total of 14 publications about 57 patients with SQSTM1-related FTD were reviewed, in which the bvFTD subtype was the main phenotype described (66.6%), with a predominance in men (63%) and positive family history in 61.4% of the cases. Conclusions: We describe a heterozygous in-frame duplication c.436_462dup p.(Pro146_Cys154dup) in the SQSTM1 gene, which affects the zinc-finger domain of p62, in a family with a personality disorder and bvFTD, expanding the genetics and clinical phenotype related to SQSTM1. © 2021 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases

Towards a Change in the Diagnostic Algorithm of Autism Spectrum Disorders: Evidence Supporting Whole Exome Sequencing as a First-Tier Test

Autism spectrum disorder (ASD) is a prevalent and extremely heterogeneous neurodevelopmental disorder (NDD) with a strong genetic component. In recent years, the clinical relevance of de novo mutations to the aetiology of ASD has been demonstrated. Current guidelines recommend chromosomal microarray (CMA) and a FMR1 testing as first-tier tests, but there is increasing evidence that support the use of NGS for the diagnosis of NDDs. Specifically in ASD, it has not been extensively evaluated and, thus, we performed and compared the clinical utility of CMA, FMR1 testing, and/or whole exome sequencing (WES) in a cohort of 343 ASD patients. We achieved a global diagnostic rate of 12.8% (44/343), the majority of them being characterised by WES (33/44; 75%) compared to CMA (9/44; 20.4%) or FMR1 testing (2/44; 4.5%). Taking into account the age at which genetic testing was carried out, we identified a causal genetic alteration in 22.5% (37/164) of patients over 5 years old, but only in 3.9% (7/179) of patients under this age. Our data evidence the higher diagnostic power of WES compared to CMA in the study of ASD and support the implementation of WES as a first-tier test for the genetic diagnosis of this disorder, when there is no suspicion of fragile X syndrome