The utility of Next Generation Sequencing for molecular diagnostics in Rett syndrome
Abstract
Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that almost exclusively affects girls and is totally disabling. Three genes have been identified that cause RTT: MECP2, CDKL5 and FOXG1. However, the etiology of some of RTT patients still remains unknown. Recently, next generation sequencing (NGS) has promoted genetic diagnoses because of the quickness and affordability of the method. To evaluate the usefulness of NGS in genetic diagnosis, we present the genetic study of RTT-like patients using different techniques based on this technology. We studied 1577 patients with RTT-like clinical diagnoses and reviewed patients who were previously studied and thought to have RTT genes by Sanger sequencing. Genetically, 477 of 1577 patients with a RTT-like suspicion have been diagnosed. Positive results were found in 30% by Sanger sequencing, 23% with a custom panel, 24% with a commercial panel and 32% with whole exome sequencing. A genetic study using NGS allows the study of a larger number of genes associated with RTT-like symptoms simultaneously, providing genetic study of a wider group of patients as well as significantly reducing the response time and cost of the study.
Full text
1 Vol.:(0123456789) Scientific Reports | (2021) 11:18146 | https://doi.org/10.1038/s41598-021-97262-y www.nature.com/scientificreports Author Correction: The utility of Next Generation Sequencing for molecular diagnostics in Rett syndrome Silvia Vidal, Núria Brandi, Paola Pacheco, Edgar Gerotina, Laura Blasco, Jean‑Rémi Trotta, Sophia Derdak, Maria del Mar O’Callaghan, Àngels Garcia‑Cazorla, Mercè Pineda, Judith Armstrong & Rett Working Group* Correction to: Scientific Reports https:// doi. org/ 10. 1038/ s4159801711620-3, published online 25 September 2017 This Article contains an error in the Acknowledgements section. “We thank all patients and their families who contribute to this study. The work was supported by grants from the Spanish Ministry of Health (Instituto de Salud Carlos III/FEDER, PI15/01013); Crowdfunding program PRECIPITA, from the Spanish Ministry of Health (Fundación Española para la Ciencia y la Tecnología); Catalan Association for Rett Syndrome; Fondobiorett and Mi Princesa Rett.” should read: “We thank all patients and their families who contribute to this study. The work was supported by grants from the Spanish Ministry of Health (Instituto de Salud Carlos III/FEDER, PI15/01159); Crowdfunding program PRECIPITA, from the Spanish Ministry of Health (Fundación Española para la Ciencia y la Tecnología); Catalan Association for Rett Syndrome; Fondobiorett and Mi Princesa Rett.” Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. © The Author(s) 2021 Rett Working Group Francisco Javier Aguirre7, Montserrat Aleu8, Xènia Alonso4, Mercè Alsius9, Maria Inmaculada Amorós10, Guillermo Antiñolo11, Lourdes Aquino12, Carmen Arellano13, Gema Arriola14, Rosa Arteaga15, Neus Baena16, Montserrat Barcos17, Nuria Belzunces18, Susana Boronat19, Tomás Camacho20, Jaume Campistol4, Miguel del Campo19, Andrea Campo11, Ramon Cancho21, Ramon Candau11, Ignacio Canós22, María del Carmen Carrascosa23, Francisco Carratalá‑Marco24, Jovaní Casano25, Pedro Castro26, Ana Cobo27, Jaime Colomer4, David Conejo28, Maria José Corrales29, Rocío Cortés30, Gabriel Cruz31, Gábor Csányi32, María Teresa de Santos33, María de Toledo34, Mireia Del Toro19, Rosario Domingo35, Anna Duat36, Rosario OPEN
2 Vol:.(1234567890) Scientific Reports | (2021) 11:18146 | https://doi.org/10.1038/s41598-021-97262-y www.nature.com/scientificreports/ Duque37, Ana María Esparza25, Rosa Fernández38, Maria Carme Fons4, Ana Fontalba15, Enrique Galán39, Pia Gallano32, María José Gamundi13, Pedro Luis García40, María del Mar García41, María García‑Barcina42, María Jesús Garcia‑Catalan4, Sixto García‑Miñaur43, Juan Jose Garcia‑Peñas36, María Teresa García‑Silva44, Rosa Gassio4, Esther Geán4, Belén Gil38, Sarenur Gökben45, Luis Gonzalez36, Veronica Gonzalez4, Julieta Gonzalez4, Gloria González18, Encarna Guillén35, Miriam Guitart16, Montserrat Guitet46, Juan Manuel Gutierrez47, Eva Gutiérrez33, Jose Luís Herranz15, Gemma Iglesias48, Iva Karacic49, Carlos H. Lahoz50, José Ignacio Lao51, Pablo Lapunzina43, María Jesús Lautre‑Ecenarro52, María Dolores Lluch53, Laura López36, Asunción López‑Ariztegui54, Alfons Macaya19, Rosario Marín55, Charles M. Lourenço Marquez56, Elena Martín44, Beatriz Martínez38, Eduardo Martínez‑Salcedo57, María José Mas58, Gonzalo Mateo14, Pilar Mendez39, Amparo Morant Jimenez59, Sira Moreno60, Fernando Mulas61, Juan Narbona62, Andrés Nascimento4, Manuel Nieto11, Tania Fabiola Nunes4, Núria Núñez19, María Obón9, Ignacio Onsurbe23, Carlos Ignacio Ortez4, Emilio Orts29, Francisco Martinez22, Rafael Parrilla63, Samuel Ignacio Pascual43, Ana Patiño64, Maria Pérez‑Poyato4, Belén Pérez‑Dueñas4, Pilar Póo4, Eliodoro Puche35, Feliciano Ramos65, Miquel Raspall19, Ana Roche4, Susana Roldan66, Jordi Rosell67, Cesar Ruiz68, María Luz Ruiz‑Falcó36, Maria Eugenia Russi4, Jordi Samarra69, Victoria San Antonio52, Ivan Sanchez4, Xavier Sanmartin4, Ana Sans4, Alfredo Santacana70, Sabine Scholl‑Bürgi71, Nuria Serrano72, Mercedes Serrano4, Pilar Martin‑Tamayo23, Adrián Tendero43, Jaime Torrents73, Diego Tortosa35, Emma Triviño74, Ledia Troncoso30, Eulalia Turrón32, Pilar Vázquez26, Carlos Vázquez70, Ramón Velázquez43, Clara Ventura19, Alfonso Verdú40, Anna Vernet4, M. Tomás Vila75 & Cristina Villar4 7Hospital Torrecardenas, Almeria, Spain. 8Consorcio Hospital General Universitario de Valencia, Valencia, Spain. 9Hospital Universitari Dr. Josep Trueta, Girona, Spain. 10Hospital Punta Europa, Cadiz, Spain. 11Hospital Universitario Virgen del Rocio, Sevilla, Spain. 12Hospital de Mataró, Mataro, Spain. 13Consorci Sanitari, Terrassa, Spain. 14Hospital universitario de Guadalajara, Guadalajara, Spain. 15Hospital Universitario Marqués de Valdecilla, Santander, Spain. 16Hospital de Sabadell, Barcelona, Spain. 17Hospital Universitario Reina Sofía, Cordoba, Spain. 18Balagué Center, Barcelona, Spain. 19Hospital de la Vall d’Hebrón, Barcelona, Spain. 20Lema & Bandin Laboratorios, Vigo, Spain. 21Hospital Universitario Río Hortega, Valladolid, Spain. 22Hospital Universitario Doctor Peset, Valencia, Spain. 23Hospital General Universitario de Albacete, Albacete, Spain. 24Hospital Universitari San Juan, Alicante, Spain. 25Hospital Universitario General de Castellón, Castellon de la Plana, Spain. 26Hospital Gregorio Marañón, Madrid, Spain. 27Hospital de Donostia, San Sebastian, Spain. 28Complejo asistencial, Burgos, Spain. 29Hospital General Mancha Centro, Ciudad Real, Spain. 30Hospital San Borja Arriaran, Santiago, Chile. 31Hospital Universitario de Valme, Sevilla, Spain. 32Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 33Hospital de Fuenlabrada, Madrid, Spain. 34Hospital Universitario Severo Ochoa, Madrid, Spain. 35Hospital Infantil de La Arrixaca, Murcia, Spain. 36Hospital Infantil Universitario Niño Jesús, Madrid, Spain. 37Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain. 38Hospital Universitario de Getafe, Madrid, Spain. 39Hospital Materno-Infantil de Badajoz, Badajoz, Spain. 40Hospital Virgen de la Salud, Toledo, Spain. 41Hospital Cormarcal de Figueres, Girona, Spain. 42Hospital de Basurto, Bilbao, Spain. 43Hospital La Paz, Madrid, Spain. 44Hospital Universitario 12 de Octubre, Madrid, Spain. 45Ege Ünŭversŭtesŭ Tip Fakültesŭ Pedŭatrŭ AD, Uzmur, Turkey. 46Hospital General de Granollers, Barcelona, Spain. 47Hospital Clínico Universitario de Valladolid, Valladolid, Spain. 48Hospital Virgen de la Luz, Cuenca, Spain. 49Clinical Hospital Center Zagreb, Zagreb, Croatia. 50Hospital Central Asturias, Asturias, Spain. 51Laboratorio Echevarne, Barcelona, Spain. 52Hospital Clínico San Carlos, Madrid, Spain. 53Hospital Universitario Virgen Macarena, Sevilla, Spain. 54Hospital de Cruces, Bilbao, Spain. 55Hospital Universitario Puerta del Mar, Cadiz, Spain. 56Medical Genetics Service, Clinics Hospital of Ribeirão Preto, University of São Paulo, Sao Paulo, Brazil. 57Hospital General Universitario de Alicante, Alicante, Spain. 58Hospital Joan XXIII, Tarragona, Spain. 59Centro privado, Valencia, Spain. 60Hospital Virgen del Camino, Pamplona, Spain. 61Instituto Valenciano de Neurociencias, Valencia, Spain. 62Clínica Universitaria de Pamplona, Pamplona, Spain. 63Complejo Hospitalario de Jaén, Jaen, Spain. 64Hospital de Navarra, Navarra, Spain. 65Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain. 66Hospital Universitario Virgen de las Nieves, Granada, Spain. 67Hospital Son Dureta, Palma de Mallorca, Spain. 68Hospital Costa del Sol, Malaga, Spain. 69Hospital General de Vic, Barcelona, Spain. 70Complejo Hospitalario Universitario Insular, Las Palmas de Gran Canaria, Spain. 71Medizinische Universität Innsbruck, Innsbruck, Austria. 72Althaia, Manresa, Spain. 73Reference Laboratory, Barcelona, Spain. 74Catlab, Barcelona, Spain. 75Hospital Francesc De Borja, Valencia, Spain.