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. 2020 Apr;97(4):610-620.
doi: 10.1111/cge.13718. Epub 2020 Feb 23.

Molecular characterization of Spanish patients with MECP2 duplication syndrome

Ainhoa Pascual-Alonso  1 , Laura Blasco  1 , Silvia Vidal  1 , Esther Gean  2 , Patricia Rubio  2 , Mar O'Callaghan  3 , Antonio F Martínez-Monseny  2 , Alba Aina Castells  1   4 , Clara Xiol  1 , Vicenç Català  5 , Nuria Brandi  6 , Paola Pacheco  6 , Carlota Ros  6 , Miguel Del Campo  7 , Encarna Guillén  8 , Salva Ibañez  8 , María J Sánchez  8 , Pablo Lapunzina  9   10 , Julián Nevado  9   10 , Fernando Santos  9 , Elisabet Lloveras  11 , Juan D Ortigoza-Escobar  3 , María I Tejada  10   12 , Hiart Maortua  10   12 , Francisco Martínez  13 , Carmen Orellana  13 , Mónica Roselló  13 , María A Mesas  14 , María Obón  15 , Alberto Plaja  16 , Joaquín A Fernández-Ramos  17 , Eduardo Tizzano  18 , Rosario Marín  19 , José L Peña-Segura  20 , Soledad Alcántara  4 , Judith Armstrong  6   10   21
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Molecular characterization of Spanish patients with MECP2 duplication syndrome

Ainhoa Pascual-Alonso et al. Clin Genet. 2020 Apr.

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: IRAK1; MECP2 duplication; Methyl-CpG-binding protein 2 (MECP2); Xq28-duplication; genotype-phenotype correlation; hypotonia; intellectual disability; recurrent infections.

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REFERENCES

    1. Ehrhart F, Coort SLM, Cirillo E, Smeets E, Evelo CT, Curfs LMG. Rett syndrome-biological pathways leading from MECP2 to disorder phenotypes. Orphanet J Rare Dis. 2016;11(1):158. https://doi.org/10.1186/s13023-016-0545-5.
    1. Sharma K, Singh J, Frost EE, Pillai PP. MeCP2 in central nervous system glial cells: current updates. Acta Neurobiol Exp (Wars). 2018;78:30-40. https://doi.org/10.21307/ane-2018-007.
    1. Horvath PM, Monteggia LM. MeCP2 as an activator of gene expression. Trends Neurosci. 2018;41(2):72-74. https://doi.org/10.1016/j.tins.2017.11.005.
    1. Villard L. MECP2 mutations in males. J Med Genet. 2007;44(7):417-423. https://doi.org/10.1136/jmg.2007.049452.
    1. Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: Revised diagnostic criteria and nomenclature. Ann Neurol. 2010;68(6):944-950. https://doi.org/10.1002/ana.22124.Rett.

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