Molecular characterization of Spanish patients with MECP2 duplication syndrome.
Ainhoa Pascual-AlonsoLaura BlascoSilvia VidalEsther GeanPatricia RubioMar O'CallaghanAntonio Federico Martínez-MonsenyAlba Aina CastellsClara XiolVicenç CatalàNuria BrandiPaola PachecoCarlota RosMiguel Del CampoEncarna GuillénSalva IbañezMaría J SánchezPablo LapunzinaJulián NevadoFernando SantosElisabet LloverasJuan D Ortigoza-EscobarMaría-Isabel TejadaHiart MaortuaFrancisco MartínezCarmen OrellanaMónica RosellóMaría A MesasMaría ObónAlberto PlajaJoaquín A Fernández-RamosEduardo F TizzanoRosario MarínJosé L Peña-SeguraSoledad AlcántaraJudith ArmstrongPublished in: Clinical genetics (2020)
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.
Keyphrases
- early onset
- intellectual disability
- autism spectrum disorder
- end stage renal disease
- high throughput
- late onset
- chronic kidney disease
- genome wide
- ejection fraction
- newly diagnosed
- high resolution
- case report
- nucleic acid
- quantum dots
- dna methylation
- hepatitis c virus
- living cells
- men who have sex with men
- single molecule
- single cell
- congenital heart disease
- hiv testing