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Int J Genomics. 2019 Mar 27;2019:6956934. doi: 10.1155/2019/6956934. eCollection 2019.

Analysis of the Phenotypes in the Rett Networked Database.

Author information

1
Medical Genetics, University of Siena, Italy.
2
Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, Wales, UK.
3
Pediatric Neurology Unit and Israeli Rett Clinic, Safra Children Hospital, Chaim Sheba Medical Center, Tel HaShomer, Israel.
4
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
5
Neurologia Fundació Sant Joan de Deu, Barcelona, Spain.
6
Pediatric Neurology, Necker-Enfants Malades Hospital, University Paris Descartes, AP-HP, Paris, France.
7
Imagine Institute, Inserm U1163, Team Genetics and Pathophysiology of the Development of Cerebral Cortex, Paris Descartes University, Paris, France.
8
INSERM, U1016, Paris, France.
9
Institute Cochin, Université Paris Descartes, CNRS, UMR8104, Paris, France.
10
Laboratoire de Biochimie et Génétique Moléculaire, Hôpital Cochin, Assistance Publique, Hôpitaux de Paris, Paris, France.
11
Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain.
12
Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain.
13
CIBER-ER (Biomedical Network Research Center for Rare Diseases), Instituto de Salud Carlos III, Madrid, Spain.
14
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
15
Child Neuropsychiatry, DINOGMI, University of Genova, Genova, Italy.
16
Istituto Auxologico Italiano, IRCCS, Laboratorio di Citogenetica e Genetica Molecolare, Cusano Milanino, Milan, Italy.
17
Epilepsy Center, Childhood and Adolescence Neurology and Psychiatry, ASST Santi Paolo Carlo, Department of Health Sciences, University of Milan, Milan, Italy.
18
Tuscany Rett Center, Ospedale Versilia, 55043 Lido di Camaiore, Italy.
19
Neurologic Department, Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic", University of Belgrade, Belgrade, Serbia.
20
Centre for Rett Syndrome, Department of Paediatrics and Adolescent Medicine, The Kennedy Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
21
Department of Neuropediatrics, Zagreb Children's Hospital, University of Zagreb, Zagreb, Croatia.
22
Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
23
All India Institute of Medical Sciences, Genetics Unit, Department of Pediatrics, New Delhi, India.
24
Child Neuropsychiatry Unit, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
25
DINOGMI, University of Genova, Genova, Italy.
26
Department of Medical Genetics, and Szentagothai Research Center, University of Pécs, Medical School, Pécs, Hungary.
27
Carol Davila University of Medicine, Pediatric Neurology Clinic, Al Obregia Hospital, Bucharest, Romania.
28
Ministry of Health, Department of Clinical Genetics, Institute of Pediatrics and Pediatric Surgery, Moscow, Russia.
29
Tri-State Rett Syndrome Center, Montefiore Medical Center, Albert Einstein College of Medicine, New York City, NY, USA.
30
Aix Marseille University, Inserm, MMG, U1251 Marseille, France.
31
Department of Medical Genetics, La Timone Children's Hospital, AP-HM, Marseille, France.

Abstract

Rett spectrum disorder is a progressive neurological disease and the most common genetic cause of intellectual disability in females. MECP2 is the major causative gene. In addition, CDKL5 and FOXG1 mutations have been reported in Rett patients, especially with the atypical presentation. Each gene and different mutations within each gene contribute to variability in clinical presentation, and several groups worldwide performed genotype-phenotype correlation studies using cohorts of patients with classic and atypical forms of Rett spectrum disorder. The Rett Networked Database is a unified registry of clinical and molecular data of Rett patients, and it is currently one of the largest Rett registries worldwide with several hundred records provided by Rett expert clinicians from 13 countries. Collected data revealed that the majority of MECP2-mutated patients present with the classic form, the majority of CDKL5-mutated patients with the early-onset seizure variant, and the majority of FOXG1-mutated patients with the congenital form. A computation of severity scores further revealed significant differences between groups of patients and correlation with mutation types. The highly detailed phenotypic information contained in the Rett Networked Database allows the grouping of patients presenting specific clinical and genetic characteristics for studies by the Rett community and beyond. These data will also serve for the development of clinical trials involving homogeneous groups of patients.

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