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Am J Med Genet A. 2016 Jan;170A(1):116-29. doi: 10.1002/ajmg.a.37384. Epub 2015 Sep 30.

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

Author information

1
FHU TRANSLAD, Centre de Référence Maladies Rares "Anomalies du Développement et Syndromes Malformatifs" de l'Est, Centre de Génétique, CHU de Dijon, France.
2
GAD, EA4271, Génétique et Anomalies du Développement, Université de Bourgogne, Dijon, France.
3
Service de Cytogénétique, CHU de Dijon, France.
4
Service de Cytogénétique, Hôpital Necker Enfants Malades, Paris, France.
5
Service de Génétique Clinique, Hôpital Necker Enfants Malades, Paris, France.
6
Service de Génétique Clinique Chromosomique et Moléculaire, CHU de Saint-Etienne, France.
7
Service de Génétique Clinique, CLAD Ouest, CHU de Rennes, France.
8
Service de Génétique Médicale, CHU de Toulouse, France.
9
Service de Génétique Médicale, CHU de Clermont-Ferrand, France.
10
Service de Neuropédiatrie et Maladies Métaboliques, Hôpital Robert Debré, Paris, France.
11
Service de Génétique Médicale, CHU de Nantes, France.
12
Service de Génétique Médicale, CHU de Nancy, France.
13
Laboratoire de Génétique Médicale, CHU de Nancy, France.
14
Service de Neuropédiatrie, CHRU de Lille, France.
15
Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre, CHRU de Lille, France.
16
Service de Génétique, CHU de Caen, France.
17
Service de Génétique, CHRU de Tours, France.
18
Service de Génétique Médicale, CHU de Rouen, France.
19
Laboratoire de Biologie Moléculaire, Hôpital Necker Enfants Malades, Paris, France.
20
Service de Neurologie Pédiatrique, CHU de Montpellier, France.
21
Service de Génétique, Centre Hospitalier de Vannes, Vannes, France.
22
Service de Génétique, Hôpital Armand Trousseau, Paris, France.
23
Laboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, Paris, France.
24
Service de Génétique Médicale, CHUV Lausanne, Lausanne, Suisse.
25
Unité de Neuropédiatrie, CHUV de Lausanne, Lausanne, Suisse.
26
Laboratoire de Cytogénétique Constitutionnelle et Prénatale, CHUV de Lausanne, Lausanne, Suisse.
27
Service de Génétique Clinique, Hôpital Robert Debré, Paris, France.
28
Laboratoire de Biologie Moléculaire, Hôpital Robert Debré, Paris, France.
29
Département de Génétique et Procréation-UMR CNRS 5525 TIMC-IMAG équipe DYCTIM, CHU Grenoble, France.
30
Service de Génétique Clinique, CHU de Bordeaux, France.
31
Département de Génétique Médicale, Hôpital de la Timone, Marseille, France.
32
Laboratoire de Génétique Chromosomique, Hôpital de la Timone, Marseille, France.
33
Laboratoire de Biologie Moléculaire, Hôpital de la Timone, Marseille, France.
34
EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, CHU de Lyon, Bron, France.
35
Service de Neurologie Pédiatrique, CHU de Lyon-GH Est, Bron, France.
36
Service de Radiologie, Hôpital Femme Mère Enfant, Bron, France.

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:

MECP2 gene; Xq28 duplication; genotype-phenotype correlation; magnetic resonance imaging

PMID:
26420639
DOI:
10.1002/ajmg.a.37384
[Indexed for MEDLINE]

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