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

Mirna Assoum; Christophe Philippe; Bertrand Isidor; Laurence Perrin; Periklis Makrythanasis; Neal Sondheimer; Caroline Paris; Jessica Douglas; Gaetan Lesca; Stylianos Antonarakis; Hanan Hamamy; Thibaud Jouan; Yannis Duffourd; Stéphane Auvin; Aline Saunier; Amber Begtrup; Catherine Nowak; Nicolas Chatron; Dorothée Ville; Kamiar Mireskandari; Paolo Milani; Philippe Jonveaux; Guylène Lemeur; Mathieu Milh; Masano Amamoto; Mitsuhiro Kato; Mitsuko Nakashima; Noriko Miyake; Naomichi Matsumoto; Amira Masri; Christel Thauvin-Robinet; Jean-Baptiste Rivière; Laurence Faivre; Julien Thevenon

doi:10.1016/j.ajhg.2016.10.009

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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

Domaine :

Sciences du Vivant [q-bio] / Médecine humaine et pathologie

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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 : mercredi 14 octobre 2020 - 03:09:07

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

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

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