The most recurrent monogenic disorders that overlap with the phenotype of Rett syndrome
Por:
Vidal-Falcó S, Brandi-Tarrau N, Pacheco-Fernández P, Maynou-Fernández J, Fernandez-Isern G, Xiol C, Pascual-Alonso A, Pineda M and Armstrong-Moron J
Publicada:
1 jul 2019
Ahead of Print:
2 may 2019
Resumen:
Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that is caused by mutations in the MECP2 gene; however, defects in other genes (CDKL5 and FOXG1) can lead to presentations that resemble classic RTT, although they are not completely identical. Here, we attempted to identify other monogenic disorders that share features of RTT. A total of 437 patients with a clinical diagnosis of RTT-like were studied; in 242 patients, a custom panel with 17 genes related to an RTT-like phenotype was run via a HaloPlex-Target-Enrichment-System. In the remaining 195 patients, a commercial TruSight-One-Sequencing-Panel was analysed. A total of 40 patients with clinical features of RTT had variants which affect gene function in six genes associated with other monogenic disorders. Twelve patients had variants in STXBP1, nine in TCF4, six in SCN2A, five in KCNQ2, four in MEF2C and four in SYNGAP1. Genetic studies using next generation sequencing (NGS) allowed us to study a larger number of genes associated with RTT-like simultaneously, providing a genetic diagnosis for a wider group of patients. These new findings provide the clinician with more information and clues that could help in the prevention of future symptoms or in pharmacologic therapy. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Filiaciones:
Vidal-Falcó S:
Sant Joan de Déu Research Foundation, Barcelona, Spain
Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain
Brandi-Tarrau N:
School of Medicine, Universitat de Barcelona, Barcelona, Spain
Pacheco-Fernández P:
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain
Maynou-Fernández J:
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain
Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain
Fernandez-Isern G:
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain
Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain
Xiol C:
Sant Joan de Déu Research Foundation, Barcelona, Spain
Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain
Pascual-Alonso A:
Sant Joan de Déu Research Foundation, Barcelona, Spain
Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain
Pineda M:
Sant Joan de Déu Research Foundation, Barcelona, Spain
Armstrong-Moron J:
Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain
CIBER-ER (Biomedical Network Research Center for Rare Diseases), Institute of Health Carlos III (ISCIII), Madrid, Spain
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