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Molecular characterization of Spanish patients with MECP2 duplication syndrome
Author(s) -
PascualAlonso Ainhoa,
Blasco Laura,
Vidal Silvia,
Gean Esther,
Rubio Patricia,
O'Callaghan Mar,
MartínezMonseny 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,
OrtigozaEscobar Juan D.,
Tejada María I.,
Maortua Hiart,
Martínez Francisco,
Orellana Carmen,
Roselló Mónica,
Mesas María A.,
Obón María,
Plaja Alberto,
FernándezRamos Joaquín A.,
Tizzano Eduardo,
Marín Rosario,
PeñaSegura José L.,
Alcántara Soledad,
Armstrong Judith
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13718
Subject(s) - multiplex ligation dependent probe amplification , gene duplication , mecp2 , hypotonia , comparative genomic hybridization , intellectual disability , genetics , medicine , phenotype , copy number variation , biology , pediatrics , gene , genome , exon
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.