Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

Details

Serval ID
serval:BIB_08C9E1B19BCA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.
Journal
American Journal of Medical Genetics. Part A
Author(s)
El Chehadeh S., Faivre L., Mosca-Boidron A.L., Malan V., Amiel J., Nizon M., Touraine R., Prieur F., Pasquier L., Callier P., Lefebvre M., Marle N., Dubourg C., Julia S., Sarret C., Francannet C., Laffargue F., Boespflug-Tanguy O., David A., Isidor B., Le Caignec C., Vigneron J., Leheup B., Lambert L., Philippe C., Cuisset J.M., Andrieux J., Plessis G., Toutain A., Goldenberg A., Cormier-Daire V., Rio M., Bonnefont J.P., Thevenon J., Echenne B., Journel H., Afenjar A., Burglen L., Bienvenu T., Addor M.C., Lebon S., Martinet D., Baumann C., Perrin L., Drunat S., Jouk P.S., Devillard F., Coutton C., Lacombe D., Delrue M.A., Philip N., Moncla A., Badens C., Perreton N., Masurel A., Thauvin-Robinet C., Des Portes V., Guibaud L.
ISSN
1552-4833 (Electronic)
ISSN-L
1552-4825
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
170A
Number
1
Pages
116-129
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.
Keywords
Adolescent, Adult, Brain Diseases/genetics, Brain Diseases/pathology, Child, Child, Preschool, Chromosomes, Human, X/genetics, Female, Gene Duplication, Genetic Association Studies, Genotype, Humans, Infant, Infant, Newborn, Magnetic Resonance Imaging/methods, Male, Mental Retardation, X-Linked/genetics, Mental Retardation, X-Linked/pathology, Methyl-CpG-Binding Protein 2/genetics, Middle Aged, Pedigree, Phenotype, Prognosis, Young Adult
Pubmed
Web of science
Create date
19/02/2016 18:07
Last modification date
20/08/2019 12:31
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