Molecular characterization of Spanish patients with MECP2 duplication syndrome

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...

Full description

Saved in:
Bibliographic Details
Published in:Clinical genetics 2020-04, Vol.97 (4), p.610-620
Main Authors: Pascual‐Alonso, Ainhoa, Blasco, Laura, Vidal, Silvia, Gean, Esther, Rubio, Patricia, O'Callaghan, Mar, Martínez‐Monseny, Antonio F., Castells, Alba Aina, Xiol, Clara, Català, Vicenç, Brandi, Nuria, Pacheco, Paola, Ros, Carlota, Campo, Miguel, Guillén, Encarna, Ibañez, Salva, Sánchez, María J., Lapunzina, Pablo, Nevado, Julián, Santos, Fernando, Lloveras, Elisabet, Ortigoza‐Escobar, Juan D., Tejada, María I., Maortua, Hiart, Martínez, Francisco, Orellana, Carmen, Roselló, Mónica, Mesas, María A., Obón, María, Plaja, Alberto, Fernández‐Ramos, Joaquín A., Tizzano, Eduardo, Marín, Rosario, Peña‐Segura, José L., Alcántara, Soledad, Armstrong, Judith
Format: Article
Language:English
Subjects:
Genetic counseling
Genotypes
genotype‐phenotype correlation
Hybridization
hypotonia
Intellectual disabilities
intellectual disability
IRAK protein
IRAK1
MECP2 duplication
MeCP2 protein
Methyl-CpG binding protein
Methyl‐CpG‐binding protein 2 (MECP2)
Neurodevelopmental disorders
Phenotypes
recurrent infections
Xq28‐duplication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0009-9163
1399-0004
DOI:10.1111/cge.13718