The utility of Next Generation Sequencing for molecular diagnostics in Rett syndrome

• Published in: Scientific reports 2017-09, Vol.7 (1), p.12288-11, Article 12288
• Main 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
• Format: Article
• Language: English
• Subjects: 45/41; 45/77; 631/208; 631/378; Age; Cohort Studies; Consortia; Cyclin-dependent kinases; DNA Copy Number Variations - genetics; Etiology; Forkhead Transcription Factors - genetics; Foxg1 protein; Genes; Genetic screening; Genetic Testing - methods; High-Throughput Nucleotide Sequencing; Hospitals; Humanities and Social Sciences; Humans; MeCP2 protein; Methyl-CpG binding protein; Methyl-CpG-Binding Protein 2 - genetics; multidisciplinary; Mutation; Nerve Tissue Proteins - genetics; Neurodevelopmental disorders; Next-generation sequencing; Patients; Polymorphism, Single Nucleotide; Protein-Serine-Threonine Kinases - genetics; Proteins; Rett syndrome; Rett Syndrome - diagnosis; Rett Syndrome - genetics; Science; Whole Exome Sequencing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-11620-3

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.