Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy

Mirna Assoum 1 Christophe Philippe 2 Bertrand Isidor 3 Laurence Perrin 4 Periklis Makrythanasis 5 Neal Sondheimer 6 Caroline Paris 7 Jessica Douglas 8 Gaetan Lesca 9, 10 Stylianos Antonarakis 5 Hanan Hamamy 5 Thibaud Jouan 1 Yannis Duffourd 1 Stéphane Auvin 4 Aline Saunier 11 Amber Begtrup 12 Catherine Nowak 8 Nicolas Chatron 9, 8 Dorothée Ville 13 Kamiar Mireskandari 6 Paolo Milani 14 Philippe Jonveaux 11 Guylène Lemeur 15 Mathieu Milh 16, 17 Masano Amamoto 18 Mitsuhiro Kato 19 Mitsuko Nakashima 19 Noriko Miyake 19 Naomichi Matsumoto 19 Amira Masri 20 Christel Thauvin-Robinet 1, 21, 4 Jean-Baptiste Rivière 1, 4 Laurence Faivre 1, 21, 4 Julien Thevenon 1, 21, 4, *
* Auteur correspondant
1 GAD - Génétique des Anomalies du Développement
2 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
3 CHU Nantes - Centre hospitalier universitaire de Nantes
4 Département de génétique [Robert Debré]
5 University of Geneva
6 Division of Clinical and Metabolic Genetics [Toronto]
7 CHRU Besançon - Centre Hospitalier Régional Universitaire [Besançon]
8 Boston Children's Hospital
9 CRNL - Centre de recherche en neurosciences de Lyon
10 UCBL - Université Claude Bernard Lyon 1
11 Service de Génétique Médicale [CHRU Nancy]
12 GeneDx [Gaithersburg, MD, USA]
13 Service de Neurologie Pédiatrique [CHU Lyon]
14 Service de Neurologie Pédiatrique, HFME, Bron, France
15 Service d'ophtalmologie [Nantes]
16 Service de pédiatrie et neurologie pédiatrique
17 GMGF - Génétique Médicale et Génomique Fonctionnelle
18 Pediatric Emergency Centre
19 YCUSM - Yokohama City University School of Medecine
20 University of Amman
21 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
Abstract : Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of AP3B2 in 86 unrelated individuals with EOEE led to the identification of an additional family. We gathered five additional families with eight affected individuals through the Matchmaker Exchange initiative by matching autosomal- recessive mutations in AP3B2. Reverse phenotyping of 12 affected individuals from eight families revealed a homogeneous EOEE phenotype characterized by severe developmental delay, poor visual contact with optic atrophy, and postnatal microcephaly. No spasticity, albinism, or hematological symptoms were reported. AP3B2 encodes the neuron-specific subunit of the AP-3 complex. Autosomal-recessive variations of AP3B1, the ubiquitous isoform, cause Hermansky-Pudlak syndrome type 2. The only isoform for the delta subunit of the AP-3 complex is encoded by AP3D1. Autosomal-recessive mutations in AP3D1 cause a severe disorder cumulating the symptoms of the AP3B1 and AP3B2 defects.
Keywords : hermansky-pudlak-syndrome intellectual disability copper-metabolism ap-4 deficiency mednik syndrome seizures mouse disorders expansion disease
Type de document :
Article dans une revue
Liste complète des métadonnées
https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01447201
Contributeur : Gad - Université de Bourgogne <>
Soumis le : jeudi 26 janvier 2017 - 16:31:27
Dernière modification le : mardi 19 novembre 2019 - 02:40:38

Lien texte intégral

openaccess

Identifiants

Collections

UNIV-BOURGOGNE | CNRS | UNIV-AMU | UNIV-ST-ETIENNE | MMG | UNIV-LORRAINE | UNIV-LYON1 | HCL | NGERE-UL | UDL

Citation

Mirna Assoum, Christophe Philippe, Bertrand Isidor, Laurence Perrin, Periklis Makrythanasis, et al.. Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy. American Journal of Human Genetics, Elsevier (Cell Press), 2016, 99 (6), pp.1368 - 1376. ⟨10.1016/j.ajhg.2016.10.009⟩. ⟨hal-01447201⟩

Exporter

BibTeX TEI DC DCterms EndNote

Partager

Métriques

Consultations de la notice

162

Contact

Informations

CCSD