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Molecular characterization of Spanish patients with MECP2 duplication syndrome |
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| Authors: | Ainhoa Pascual-Alonso Laura Blasco Silvia Vidal Esther Gean Patricia Rubio Mar O'Callaghan Antonio F. Martínez-Monseny Alba Aina Castells Clara Xiol Vicenç Català Nuria Brandi Paola Pacheco Carlota Ros Miguel del Campo Encarna Guillén Salva Ibañez María J. Sánchez Pablo Lapunzina Julián Nevado Fernando Santos Elisabet Lloveras Juan D. Ortigoza-Escobar María I. Tejada Hiart Maortua Francisco Martínez Carmen Orellana Mónica Roselló María A. Mesas María Obón Alberto Plaja Joaquín A. Fernández-Ramos Eduardo Tizzano Rosario Marín José L. Peña-Segura Soledad Alcántara Judith Armstrong |
| Affiliation: | 1. Fundación San Juan de Dios, Servicio de Medicina Genética y Molecular, Barcelona, Spain;2. Departamento de Medicina Genética y Molecular, Hospital Universitario San Juan de Dios, Barcelona, Spain;3. Departamento de Neurología Pediátrica, Hospital Universitario San Juan de Dios, Barcelona, Spain;4. Fundación San Juan de Dios, Servicio de Medicina Genética y Molecular, Barcelona, Spain Neural Development Lab, Departament de Patologia i Terapèutica Experimental, Institut de Neurociències, Universitat de Barcelona, IDIBELL, l'Hospitalet de Llobregat, Barcelona, Spain;5. Unitad de Biología Celular y Genética Médica, Departament of BCFyI, Universidad Autónoma de Barcelona, Barcelona, Spain;6. Servicio de Medicina Genètica i Molecular, Hospital Universitario San Juan de Dios, Barcelona, Spain;7. Pediatrics, Genetic Epidemiology, Hospital Valle Hebrón, Barcelona, Spain;8. Unidad de Genética, Hospital Virgen de la Arrixaca, Murcia, Spain;9. Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid, Spain CIBERER (Biomedical Network Research Center for Rare Diseases), Instituto de Salud Carlos III, Madrid, Spain;10. Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid, Spain;11. Departamento de Genètica, LABCO-Iberia, Barcelona, Spain;12. CIBERER (Biomedical Network Research Center for Rare Diseases), Instituto de Salud Carlos III, Madrid, Spain;13. CIBERER (Biomedical Network Research Center for Rare Diseases), Instituto de Salud Carlos III, Madrid, Spain Laboratorio de Genética Molecular, Servicio de Genética, Instituto de Investigación Sanitaria Biocruces, Hospital Universitario de Cruces, Barakaldo, Spain;14. Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain;15. Gastroenterologia, Hospital Xanit, Málaga, Spain;16. Area de Genètica Clínica i Consell Genètic, Laboratoris ICS, Girona, Spain;17. Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Hospital Universitari Vall d'Hebron, Barcelona, Spain;18. Unidad de Neuropediatría, Hospital Universitario Reina Sofía, Córdoba, Spain;19. Area Genética Clínica y Molecular, Hospital Universitari Vall d'Hebron, Barcelona, Spain;20. Hospital Universitario Puerta del Mar Unidad de Genética, Cádiz, Spain;21. Unidad de Neuropediatría, Hospital Universitario Miguel Servet, Zaragoza, Spain;22. Neural Development Lab, Departament de Patologia i Terapèutica Experimental, Institut de Neurociències, Universitat de Barcelona, IDIBELL, l'Hospitalet de Llobregat, Barcelona, Spain |
| Abstract: | MECP2 duplication syndrome (MDS) is an X-linked neurodevelopmental disorder characterized by a severe to profound intellectual disability, early onset hypotonia and diverse psycho-motor and behavioural features. To date, fewer than 200 cases have been published. We report the clinical and molecular characterization of a Spanish MDS cohort that included 19 boys and 2 girls. Clinical suspicions were confirmed by array comparative genomic hybridization and multiplex ligation-dependent probe amplification (MLPA). Using, a custom in-house MLPA assay, we performed a thorough study of the minimal duplicated region, from which we concluded a complete duplication of both MECP2 and IRAK1 was necessary for a correct MDS diagnosis, as patients with partial MECP2 duplications lacked some typical clinical traits present in other MDS patients. In addition, the duplication location may be related to phenotypic severity. This observation may provide a new approach for genotype-phenotype correlations, and thus more personalized genetic counselling. |
| Keywords: | genotype-phenotype correlation hypotonia intellectual disability IRAK1 MECP2 duplication Methyl-CpG-binding protein 2 (MECP2) recurrent infections Xq28-duplication |