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 δ 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.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Assoum M,Philippe C,Isidor B,Perrin L,Makrythanasis P,Sondheimer N,Paris C,Douglas J,Lesca G,Antonarakis S,Hamamy H,Jouan T,Duffourd Y,Auvin S,Saunier A,Begtrup A,Nowak C,Chatron N,Ville D,Mireskandari K,Milani Pdoi
10.1016/j.ajhg.2016.10.009subject
Has Abstractpub_date
2016-12-01 00:00:00pages
1368-1376issue
6eissn
0002-9297issn
1537-6605pii
S0002-9297(16)30445-1journal_volume
99pub_type
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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