The utility of Next Generation Sequencing for molecular diagnostics in Rett syndrome
Authors: Vidal Silvia , Brandi Núria , Pacheco Paola , Gerotina Edgar , Blasco Laura , Trotta Jean-Rémi , Derdak Sophia , del Mar O’Callaghan Maria , Garcia-Cazorla Àngels , Pineda Mercè , Armstrong Judith ,   Rett Working Group, Aguirre Francisco Javier , Aleu Montserrat , Alonso Xènia , Alsius Mercè , Inmaculada Amorós Maria , Antiñolo Guillermo , Aquino Lourdes , Arellano Carmen , Arriola Gema , Arteaga Rosa , Baena Neus , Barcos Montserrat , Belzunces Nuria , Boronat Susana , Camacho Tomás , Campistol Jaume , del Campo Miguel , Campo Andrea , Cancho Ramon , Candau Ramon , Canós Ignacio , Carrascosa María del Carmen , Carratalá-Marco Francisco , Casano Jovaní , Castro Pedro , Cobo Ana , Colomer Jaime , Conejo David , Corrales Maria José , Cortés Rocío , Cruz Gabriel , Csányi Gábor , de Santos María Teresa , de Toledo María , Toro Mireia Del , Domingo Rosario , Duat Anna , Duque Rosario , Esparza Ana María , Fernández Rosa , Fons Maria Carme , Fontalba Ana , Galán Enrique , Gallano Pia , Gamundi María José , García Pedro Luis , García María del Mar , García-Barcina María , Garcia-Catalan María Jesús , García-Miñaur Sixto , Garcia-Peñas Juan Jose , García-Silva María Teresa , Gassio Rosa , Geán Esther , Gil Belén , Gökben Sarenur , Gonzalez Luis , Gonzalez Veronica , Gonzalez Julieta , González Gloria , Guillén Encarna , Guitart Miriam , Guitet Montserrat , Gutierrez Juan Manuel , Gutiérrez Eva , Herranz Jose Luís , Iglesias Gemma , Karacic Iva , Lahoz Carlos H. , Lao José Ignacio , Lapunzina Pablo , Lautre-Ecenarro María Jesús , Lluch María Dolores , López Laura , López-Ariztegui Asunción , Macaya Alfons , Marín Rosario , Marquez Charles M. Lourenço , Martín Elena , Martínez Beatriz , Martínez-Salcedo Eduardo , Mas María José , Mateo Gonzalo , Mendez Pilar , Jimenez Amparo Morant , Moreno Sira , Mulas Fernando , Narbona Juan , Nascimento Andrés , Nieto Manuel , Nunes Tania Fabiola , Núñez Núria , Obón María , Onsurbe Ignacio , Ortez Carlos Ignacio , Orts Emilio , Martinez Francisco , Parrilla Rafael , Pascual Samuel Ignacio , Patiño Ana , Pérez-Poyato Maria , Pérez-Dueñas Belén , Póo Pilar , Puche Eliodoro , Ramos Feliciano , Raspall Miquel , Roche Ana , Roldan Susana , Rosell Jordi , Ruiz Cesar , Ruiz-Falcó María Luz , Russi Maria Eugenia , Samarra Jordi , Antonio Victoria San , Sanchez Ivan , Sanmartin Xavier , Sans Ana , Santacana Alfredo , Scholl-Bürgi Sabine , Serrano Nuria , Serrano Mercedes , Martin-Tamayo Pilar , Tendero Adrián , Torrents Jaime , Tortosa Diego , Triviño Emma , Troncoso Ledia , Turrón Eulalia , Vázquez Pilar , Vázquez Carlos , Velázquez Ramón , Ventura Clara , Verdú Alfonso , Vernet Anna , Vila M. Tomás , Villar Cristina 
Published: September 2017

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.