IQSEC2 disorder: A new disease entity or a Rett spectrum continuum?
Por:
Lopergolo D, Privitera F, Castello G, Lo Rizzo C, Mencarelli MA, Pinto AM, Ariani F, Currò A, Lamacchia V, Canitano R, Vaghi E, Ferrarini A, Baltodano GM, Lederer D, Van Maldergem L, Serrano M, Pineda M, Fons-Estupina MDC, Van Esch H, Breckpot J, Kumps C, Callewaert B, Mueller S, Ramelli GP, Armstrong-Moron J, Renieri A and Mari F
Publicada:
1 mar 2021
Ahead of Print:
1 ene 2021
Resumen:
IQSEC2 mutations are associated with IQSEC2-related intellectual disability (ID). Phenotypic spectrum has been better defined in the last few years by the increasing number of reported cases although the genotype-phenotype relationship for IQSEC2 remains overall complex. As for IQSEC2-related ID a wide phenotypic diversity has been described in Rett syndrome (RTT). Several patients harboring IQSEC2 mutations present with clinical symptoms similar to RTT and some cases meet most of the criteria for classic RTT. With the aim of establishing a genotype-phenotype correlation, we collected data of 16 patients harboring IQSEC2 point mutations (15 of them previously unreported) and of five novel patients carrying CNVs encompassing IQSEC2. Most of our patients surprisingly shared a moderate-to-mild phenotype. The similarities in the clinical course between our mild cases and patients with milder forms of atypical RTT reinforce the hypothesis that also IQSEC2 mutated patients may lay under the wide clinical spectrum of RTT and thus IQSEC2 should be considered in the differential diagnosis. Our data confirm that position, type of variant and gender are crucial for IQSEC2-associated phenotype delineation.
Filiaciones:
Lopergolo D:
Medical Genetics, University of Siena, Siena, Italy
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Privitera F:
Medical Genetics, University of Siena, Siena, Italy
Castello G:
Medical Genetics, University of Siena, Siena, Italy
Lo Rizzo C:
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Mencarelli MA:
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Pinto AM:
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Ariani F:
Medical Genetics, University of Siena, Siena, Italy
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Currò A:
Medical Genetics, University of Siena, Siena, Italy
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Lamacchia V:
Medical Genetics, University of Siena, Siena, Italy
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Canitano R:
Division of Child and Adolescent Neuropsychiatry, University Hospital of Siena, Siena, Italy
Vaghi E:
MAS Clinica Generale, Istituto Oncologico della Svizzera Italiana, Ospedale Regionale di Lugano, Italiano, Lugano, Switzerland
Ferrarini A:
Chief Medical Genetics EOC, CSSI- Ospedale Regionale di Lugano, Italiano, Lugano, Switzerland
Baltodano GM:
Departamento de Genética, Hospital Infantil Manuel de Jesús Rivera, Managua, Nicaragua
Lederer D:
Department of Clinical Genetics, Centre for Human Genetics, Gosselies, Belgium
Van Maldergem L:
Center of Human Genetics, University of Franche-Comté, Besançon, France
Serrano M:
Pediatric Neurology Department, Hospital Sant Joan de Déu, Institut de Recerca, Barcelona, Spain
U-703 CIBERER, Instituto de Salud Carlos III, Barcelona, Spain
Pineda M:
Department of Neuropediatria, Fundación Sant Joan de Déu, Barcelona, Spain
Fons-Estupina MDC:
U-703 CIBERER, Instituto de Salud Carlos III, Barcelona, Spain
Pediatric Neurology Department, Fetal-Neonatal Neurology Unit and Early Onset Epilepsy, Hospital Sant Joan de Déu, Institut de Recerca, Barcelona, Spain
Van Esch H:
Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium
Breckpot J:
Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium
Kumps C:
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
Callewaert B:
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
Mueller S:
Pediatric Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Ramelli GP:
Pediatric Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Armstrong-Moron J:
Genetics Department, Hospital Sant Joan de Deu, Institut Pediàtric de Recerca and CIBERER, Barcelona, Spain
Renieri A:
Medical Genetics, University of Siena, Siena, Italy
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Mari F:
Medical Genetics, University of Siena, Siena, Italy
Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy
Green Submitted, Bronze
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